Review Articles

Resident Macrophages in Cystic Kidney Disease

Zhang Li, Kurt A. Zimmerman and Bradley K. Yoder
Kidney360 January 2021, 2 (1) 167-175; DOI: https://doi.org/10.34067/KID.0006052020

Abstract

Interstitial inflammation is an important feature of cystic kidney disease. Renal macrophages are the most well-studied inflammatory cell in the kidney, and their involvement in cyst formation has been reported in different animal models and patients with cystic kidney disease. Originally, it was believed that renal macrophages were maintained from a constant supply of bone marrow–derived circulating monocytes, and could be recruited to the kidney in response to local inflammation. However, this idea has been challenged using fate-mapping methods, by showing that at least two distinct developmental origins of macrophages are present in the adult mouse kidney. The first type, infiltrating macrophages, are recruited from circulating monocytes and gradually develop macrophage properties on entering the kidney. The second, resident macrophages, predominantly originate from embryonic precursors, colonize the kidney during its development, and proliferate in situ to maintain their population throughout adulthood. Infiltrating and resident macrophages work together to maintain homeostasis and properly respond to pathologic conditions, such as AKI, cystic kidney disease, or infection. This review will briefly summarize current knowledge of resident macrophages in cystic kidney disease.

Macrophages in Kidney

Renal macrophages, the largest population of immune cells in kidney, play a critical role in homeostasis, surveillance, immune response, tissue injury, and repair (1⇓–3). Macrophages are a major constituent of the renal mononuclear phagocyte system and were believed to arise from bone marrow–derived monocytes that could be polarized into different phenotypic subsets in response to environmental stimuli (4⇓–6). However, they were often confused with dendritic cells due to their shared cell-surface expression of CD11c and MHCII (7,8). With the advent of new lineage tracing and single-cell RNA sequencing approaches, it is now possible to clearly delineate macrophages and dendritic cells in the kidney across mammalian species (9⇓–11). In these studies, the authors demonstrated that renal macrophages were highly heterogenous and specialized populations and were derived from two different developmental origins (12⇓–14) (Figure 1). One type, infiltrating macrophages, is derived from monocyte precursors in the bone marrow and recruited to the kidney in response to local inflammation (15,16). The other type, resident macrophages, maintain long-term residency in kidney with less mobility and arise primarily during organogenesis (17). They are derived in a Myb-independent manner from erythromyeloid progenitors that are first generated in the fetal yolk sac, colonize the fetal liver, and migrate into the kidney during early development (12,13,17).

Figure 1.
Figure 1.

The origins of macrophages in kidney. Two types of macrophages are present in the adult mouse kidney. Resident macrophages predominantly originate from embryonic precursors, migrate into the kidney during early development, and are maintained in the kidney through local proliferation. Infiltrating macrophages are derived from monocyte precursors in the bone marrow, and are recruited to the kidney in response to local inflammation. The dashed arrow indicates a limited but continuous contribution of monocyte-derived cells to the resident-macrophage pool in adult mouse kidneys.

The idea that resident macrophages are a homogenous population in the kidney and are exclusively derived from embryonic precursors has recently been challenged. Utilizing a newly generated cre-induced-hCD59 transgenic line, Liu et al. (18) traced the fate of resident macrophages in the kidney from birth to full maturity, and found that a portion of resident macrophages are actually derived from peripheral monocytes. The idea that some kidney-resident macrophages are derived from monocytes was supported by data from Ms4a3Cre-RosaTdT fate-mapping mice, which faithfully label all adult hematopoietic stem cell–derived monocytes (19). In these studies, the authors showed that a significant portion of kidney-resident macrophages were originated from adult hematopoietic stem cell–derived monocytes. Liu et al. (18) also demonstrated that both lineages of resident macrophages shared the feature of long-lived residency in the kidney, but had functional differences in aspects including immune response and metabolic profile in disease conditions. These data suggest kidney-resident macrophages can be derived from multiple precursor populations and their ontological origin may influence their function (6,17,18).

In mice, infiltrating and resident macrophages can be distinguished on the basis of the expression of surface markers F4/80 and CD11b, with resident macrophages being F4/80high, CD11blow and infiltrating macrophages being F4/80low, CD11bhigh (12,13,20). The exact function of resident macrophages in the kidney is not well known, although emerging evidence suggests they play an important role in kidney development, vascularization, and renal repair in response to AKI (17,21⇓⇓–24). Although there are limited data on the function of resident macrophages in the kidney, in part due to the nonspecific approaches used to study these cells in the past, we may be able to gain insight into their proposed functions due to similarities between M2-like macrophages and resident macrophages. M2 macrophages have an anti-inflammatory and profibrotic function (3,4,25); most resident macrophages also exhibit an M2-like phenotype, with intrinsic anti-inflammatory properties (3). In addition, renal resident macrophages share expression of CD206 and Arg1 with M2 macrophages (20,26), suggesting that M2 macrophages and resident macrophages are similar populations of cells. It has also been reported that CD206+ M2 macrophages can promote tubular regeneration by expressing growth factors during the reparative phase after AKI, which is similar to the function of resident macrophages in AKI (27⇓–29). Although these cells share significant functional properties, direct evidence that M2 macrophages and resident macrophages are the same cell type is still lacking.

Overall, it is evident the renal macrophage niche in the kidney is more diverse than originally appreciated. To better understand the role of macrophages in kidney under normal and pathologic conditions, further studies are needed to characterize the respective functions of these macrophage subsets and the underlying molecular mechanisms involved.

Macrophages in Cystic Kidney Disease

Seminal studies in the field of cystic kidney disease highlighted an association between the number of renal macrophages and the severity of cystic disease (30⇓⇓–33). However, it was debated whether macrophages had a causative role in cyst formation or were a secondary consequence of cyst progression and expansion. Karihaloo et al. (34) provided the first evidence that macrophages could promote cyst progression in animal models utilizing a phagocytic poison, liposomal clodronate (LC), to deplete all macrophages in the kidney. The authors showed that treatment of cystic mice with LC not only significantly decreased the number of renal macrophages (95% reduction), but more importantly, reduced the cystic index and improved renal function when compared with vehicle-treated controls (Table 1). The conclusion that macrophages could promote cystic kidney disease was further supported by subsequent studies from Swenson-Fields et al. (35). In these studies, the authors showed that treatment with LC also reduced cystic disease in a recessive model of cystic kidney disease. These data suggested macrophages may be involved in promoting cyst progression in multiple forms of cystic kidney disease. However, because these studies removed all phagocytic cells in the kidney, which includes infiltrating macrophages, resident macrophages, and dendritic cells, the contribution of each subset to cyst progression was still unknown.

View this table:
Table 1.

Effect of macrophage interventions on cystic kidney disease and their outcomes

There was a long-held belief that renal macrophages are derived from, and continually replenished by, circulating monocytes. This has led to the idea that targeting the recruitment of monocytes to the kidney may be therapeutically beneficial in the context of cystic kidney disease. This hypothesis is supported by data indicating that genetic deletion or pharmacologic inhibition of Ccl2 (also known as monocyte chemoattractant-1 or MCP-1) and macrophage migration inhibitory factor reduce the severity of cystic kidney disease (36⇓–38). More importantly, the level of cyst reduction using macrophage-targeted therapeutics was comparable to other inhibitors commonly used in the PKD field, such as tolvaptan or rapamycin (39,40). Whereas several studies indicate that inhibition of these macrophage ligand:receptor interactions restricts cyst growth, other studies did not report similar findings (41⇓–43). The involvement of infiltrating macrophages in cystic disease remains controversial, and has been reviewed previously (44⇓⇓–47). For comparison, we include a table that summarizes the outcomes from multiple studies targeting macrophages in cyst severity (Table 1).

Resident-Macrophage Involvement in Cystic Kidney Disease

In retrospect, data suggested the presence and involvement of resident macrophages in cystic kidney disease for several decades. For example, multiple studies indicate that alternatively activated M2-like macrophages expressing CD206 (26,35,48), a newly identified cross-species marker of resident macrophages (11,49), could promote renal cyst formation. Microarray analysis from Mrug et al. (50) found that in a nonorthologous model of autosomal recessive polycystic kidney disease (Cys1cpk/cpk), the most highly expressed genes were those associated with the innate immune response. Of interest, several of these innate immune genes were recently identified as being specific for resident macrophages by single-cell RNA sequencing (C1qa, Cxcl16) (11). Also, Viau et al. (36) found increased numbers of both infiltrating and resident macrophages during cyst progression in inducible Lkb1 and Pkd1 mouse models. Although the authors emphasized the importance of infiltrating macrophages in controlling cyst progression in this study, they also observed an increased number of resident macrophages expressing CCR2 (receptor for MCP-1) in cystic kidneys, suggesting the MCP1-CCR2 axis may also be important for resident macrophages.

Zimmerman et al. (20) provided evidence for the involvement of resident macrophages in cystic disease using conditional Ift88 cilia mutant mice. These mutants develop a cystic kidney disease phenotype, where the severity is greatly influenced by the age at which cilia loss is induced (51). Ift88 loss induced in juvenile periods (before postnatal day 14) leads to rapid and severe cyst formation. In contrast, induction in adults results in slow cyst progression occurring in focal regions of the kidney. The rate of cyst formation in adult-induced mutants was found to be greatly increased and more widespread after ischemia-reperfusion injury. In correlation with these rates of cystogenesis, the authors showed that resident macrophages in wild-type mouse kidneys undergo a phenotypic switch (from CD11clow to CD11chigh) during the postnatal period. CD11clow resident macrophages are enriched during juvenile periods, negligible in adult mice, and reappeared after renal ischemia-reperfusion injury in adult cilia mutant mice. More importantly, the number of CD11clow resident macrophages was increased before and during cyst formation, suggesting a potential causative or at least contributing role for these cells in cyst formation. Analysis of confocal images indicated most resident macrophages coexpressed F4/80, Ki67, and CD206 in cystic regions, suggesting a reciprocal communication between resident macrophages and cyst-lining epithelial cells (Figure 2). To understand the mechanism through which resident macrophages were accumulating, the authors performed parabiosis experiments by joining the circulation of a CD45.2 control or cilia mutant mouse with a congenic CD45.1 wild-type mouse and found the accumulation of resident macrophages in cilia mutant kidneys was independent of peripheral blood input. Analysis of cell proliferation using Ki67 indicated that accumulation of resident macrophages in injured cilia mutant mice was largely driven by self-proliferation. To determine the cell type that was responsible for driving resident macrophage proliferation, the authors flow sorted epithelial populations and showed the expression of membrane-bound colony stimulation factor 1 was significantly increased in the proximal tubule cells of the injured cilia mutant kidneys compared with injured controls (Figure 2). Inhibition of CSF1R kinase signaling, using GW2580 (52), reduced resident macrophage proliferation, prevented the accumulation of CD11clow resident macrophages, and reduced the severity of cystic disease in the injured conditional Ift88 model and in the more rapidly progressing cpk mouse model. Interestingly, GW2580 treatment did not affect the infiltrating macrophage number, suggesting the effects of GW2580 were resident-macrophage specific.

Figure 2.
Figure 2.

Proposed functions of resident macrophages during cyst formation and expansion. Multiple processes occur during cyst formation and expansion, including increased epithelial proliferation and apoptosis, interstitial inflammation, increased extracellular matrix deposition and renal fibrosis, and vasculature abnormalities. Resident macrophages may be involved in controlling several of these processes directly or indirectly. It has been proposed that resident macrophages can promote cystic epithelial proliferation by secretion of cytokines and phagocytosis of apoptotic epithelial cells. Also, renal-resident macrophages may drive interstitial myofibroblast activation and proliferation, leading to increased extracellular matrix deposition and renal fibrosis. Resident macrophages may serve as “first responders” in the kidney and control the accumulation and effector function of other immune cells, such as neutrophils, infiltrating macrophages, and T cells, to indirectly regulate cyst formation. Finally, renal resident macrophages may also regulate vasculature abnormalities through their proposed proangiogenic functions. The inset indicates the reciprocal communication between resident macrophages and the cilia mutant epithelium via mb-CSF1/CSF-1R. ECM, extracellular matrix; mb-CSF1, membrane-bound colony-stimulating factor-1; RM, resident macrophages; IM, infiltrating macrophages.

Data showing that resident macrophages could promote cystic disease were supported by follow-up studies investigating the involvement of macrophage subsets in an orthologous mouse model of autosomal dominant polycystic kidney disease (ADPKD) (53). Using conditional Pkd1 mice with unilateral nephrectomy, Zimmerman and colleagues showed the numbers of infiltrating and resident macrophages were increased in conditional Pkd1 mice with unilateral nephrectomy compared with sham-operated mice, and that the increase occurred before the onset of severe cystogenesis. Furthermore, the authors showed that IFN regulatory factor 5 (Irf5), a transcription factor known to induce inflammatory cytokine production in macrophages (54), was increased in infiltrating and resident macrophages in cystic kidneys. To identify the function of IRF5 in macrophages and its importance in cyst formation, the authors suppressed the expression of IRF5 with an antisense oligo (ASO) treatment and found that IRF5 suppression decreased the number of kidney-resident macrophages, reduced inflammatory gene expression, and reduced cyst growth. More careful characterization of infiltrating and resident macrophages showed that IRF5 ASO treatment specifically reduced Irf5 and Il6 expression in resident macrophages, but did not affect their expression in infiltrating macrophages. More importantly, the authors found that IRF5 ASO-treated mice have reduced STAT3 phosphorylation and expression of p-STAT3 target genes compared with vehicle treated mice suggesting that IRF5-expressing resident macrophages released inflammatory cytokines (IL-6) stimulating STAT3 phosphorylation in the epithelium thereby promoting cyst growth in mice lacking Pkd1.

The data presented in this review suggest the involvement of resident macrophages in cystic kidney disease. However, the exact mechanism by which resident macrophages influence cyst growth is largely unknown. Although Zimmerman and colleagues provided evidence that cytokines such as IL6 may influence cyst growth through a STAT-dependent mechanism, other direct or indirect mechanisms are likely involved in regulating cyst formation and disease progression (55) (Figure 2). For example, resident macrophages control injury and repair processes in the kidney by promoting tubular epithelial cell proliferation and de-differentiation, which are hallmarks of renal cyst formation (55). RNA sequencing of resident macrophages after AKI indicated transcriptional reprogramming of resident macrophages, including upregulation of several Wnt genes (Wnt4, Wnt7b, Wnt10a, and Wnt10b) (21). Wnt-induced β-catenin signaling can protect against epithelial apoptosis and promote proliferative repair (27,56,57). In addition, Wnt signaling can also drive interstitial myofibroblast activation and proliferation, leading to increased matrix-protein deposition and renal fibrosis (56,58). These data suggest that resident macrophage–derived Wnts promote the proliferation of cystic epithelium and drive interstitial fibrosis during cystic disease progression.

It is also possible that resident macrophages serve as “first responders” in the kidney and control the accumulation and effector function of other immune cells, such as neutrophils, infiltrating macrophages, and T cells, which have all been observed in patients and mouse models of cystic kidney disease (47,59⇓⇓–62). In fact, resident macrophages are well suited for this role as they are able to maintain a persistent residence in an adult kidney through self-proliferation and are located directly adjacent to the tubular epithelium (63). Thus, they may serve as sentinels in the kidney to regulate the accumulation of other immune cells that influence cyst growth and progression. Indeed, due to their residency advantage, resident macrophages can act more rapidly than neutrophils, which have always been regarded as first responders in kidney injury. Using a combination of intravital imaging and confocal multiplex microscopy, Uderhardt et al. (24) observed that resident macrophages exert a “cloaking” behavior by extending pseudopods around a local injury, which will prevent injury-induced neutrophil activation and neutrophil-driven inflammation. Thus, it is possible resident macrophages serve a similar role in cystic disease.

In addition, epithelial apoptosis is detected during cyst formation (64) and macrophages are known to be professional phagocytes. Thus, resident macrophages may control cyst growth through phagocytosis of damaged epithelial cells and subsequent activation of inflammatory signaling pathways. This is supported by data showing that resident macrophages can detect and scavenge immune complexes or foreign debris in the interstitium, and upregulate several inflammatory signaling pathways including NF‐κB and JAK/STAT, both of which are associated with worsened cystic disease (22,65).

Moreover, resident macrophages could also contribute to cyst progression through other mechanisms, including regulation of vasculature abnormalities through their proposed proangiogenic functions (23,66,67). It is also possible resident macrophages directly or indirectly regulate fluid secretion as data suggest macrophage-derived cytokines mediate the localization and activity of multiple ion channels in kidney and other tissues (68⇓⇓–71). All of these processes have been reported to be involved in cystic kidney disease (72,73).

Targeting Resident Macrophages as a Potential Therapeutic Intervention

Inhibition or reduction of resident-macrophage numbers has beneficial effects both on cyst burden and disease progression in multiple preclinical models (20,53). However, because the mechanism of resident-macrophage involvement in cyst growth is unknown, and the approaches for identifying these cells across species are difficult, there have been significant limitations in targeting these cells in patients with cystic kidney disease. Despite these limitations, it should be noted that inhibition of two proinflammatory signaling pathways that are present in resident macrophages, the NF‐κB and JAK/STAT pathway, has significantly ameliorated cystic severity in animal models (45,46). For example, a STAT3 inhibitor, S3I‐201, significantly inhibited cyst formation and growth in a neonatal PKD mouse model (74). In addition, triptolide has well-known anti-inflammatory effects through inhibiting NF‐κB transactivation and its beneficial effect on cystogenesis in ADPKD mouse models has been reported for decades (75,76). Results from a phase 3 clinical trial of triptolide in ADPKD (NCT02115659) are much anticipated (https://clinicaltrials.gov/ct2/show/NCT02115659).

Another caveat to understanding resident-macrophage involvement is the difficulty of translating resident-macrophage–focused animal studies to humans. This difficulty is due to the fact that markers used to delineate mouse macrophages (i.e., F4/80) are not expressed by their human counterparts, making it challenging to identify analogous populations between species. Also, due to the lack of an appropriate method, there is no way to distinguish monocyte-derived infiltrating macrophages from embryonically seeded resident macrophages in the human kidney. Utilizing the recently developed single-cell RNA sequencing technique, Zimmerman et al. (11) identified a cross-species kidney resident-macrophage–specific gene expression signature by sequencing CD45+ cells isolated from mouse, rat, pig, and human kidney tissue. As part of this signature, the authors identified C1QC, CD81, and CD74 as novel, cross-species markers of resident macrophages. The authors went on to show these markers were expressed in mouse resident macrophages at the protein level, and were coexpressed at the protein level in a population of CD45+ cells isolated from rats and humans. Thus, it is likely that resident macrophages are present in other species and C1q, CD81, and CD74 can be used to identify these cells.

The identification of resident macrophages in human kidneys will greatly facilitate clinically relevant translational research from murine models to human patients. Macrophage targeting as a potential therapeutic intervention has been implicated and has led to promising results in preclinical models of inflammatory diseases and cancer (77). However, specifically targeting resident macrophages in the kidney of patients is extremely challenging, due to the lack of precise approaches to deplete kidney resident macrophages from their useful counterparts in other tissues. Thus, any resident-macrophage inhibitors would deplete resident macrophages in all tissues where they are essential for basic biologic functions such as synapse pruning, cardiac electrical conduction, and preventing infections (78,79). Therefore, it is critical to develop kidney-specific approaches to selectively deplete resident macrophages.

Conclusions and Future Perspectives

In summary, studies have shown the involvement of renal resident macrophages in cyst progression and that targeting resident macrophages using genetic deletion or pharmacologic inhibition is a promising therapeutic target for reducing cyst growth. Understating the function of resident macrophages in physiologic and pathologic conditions is important to reveal their mechanism of action in cystic kidney disease and translate these novel mechanisms to benefit patients with cystic kidney disease.

Disclosures

All authors have nothing to disclose.

Funding

These studies were supported in part by University of Alabama at Birmingham (UAB) School of Medicine AMC21 grant (to B.K. Yoder); Polycystic Kidney Disease Research Foundation grant 214g16a (to B.K. Yoder); National Institute of Diabetes and Digestive and Kidney Diseases grants R01DK115752 (to B.K. Yoder) and K01DK119375 (to K.A. Zimmerman); a pilot and feasibility grant from the Baltimore PKD Center 2P30DK090868 (to K.A. Zimmerman); a pilot grant from the UAB Hepato/Renal Fibrocystic Disease Core Center 5P30DK074038 (to K.A. Zimmerman); a seed grant from the Presbyterian Health Foundation (to K.A. Zimmerman); and a pilot grant from Oklahoma Center for Microbial Pathogenesis and Immunity (1P20GM134973; to K.A. Zimmerman).

Acknowledgments

The authors are thankful to Dr. Courtney Haycraft and members of Dr. B.K. Yoder’s laboratory for providing insightful comments during the preparation of this manuscript. Figures in this review were created with BioRender.com.

Author Contributions

Z. Li, B.K. Yoder and K.A. Zimmerman conceptualized the study, wrote the original draft, and reviewed and edited the manuscript; B.K. Yoder and Z. Li were responsible for funding acquisition; and Z. Li prepared the figures.

  • Received October 13, 2020.
  • Accepted December 10, 2020.

References

  1. ↵
    1. Duffield JS
    : Macrophages and immunologic inflammation of the kidney. Semin Nephrol 30: 234–254, 2010 https://doi.org/10.1016/j.semnephrol.2010.03.003
    OpenUrlCrossRefPubMed
  2. ↵
    1. Baek J-H
    : The impact of versatile macrophage functions on acute kidney injury and its outcomes. Front Physiol 10: 1016, 2019 https://doi.org/10.3389/fphys.2019.01016
    OpenUrl
  3. ↵
    1. Chen T,
    2. Cao Q,
    3. Wang Y,
    4. Harris DCH
    : M2 macrophages in kidney disease: Biology, therapies, and perspectives. Kidney Int 95: 760–773, 2019 https://doi.org/10.1016/j.kint.2018.10.041
    OpenUrlCrossRef
  4. ↵
    1. Italiani P,
    2. Boraschi D
    : From monocytes to M1/M2 macrophages: Phenotypical vs. functional differentiation. Front Immunol 5: 514, 2014 https://doi.org/10.3389/fimmu.2014.00514
    OpenUrlCrossRefPubMed
  5. ↵
    1. Murray PJ
    : Macrophage polarization. Annu Rev Physiol 79: 541–566, 2017 https://doi.org/10.1146/annurev-physiol-022516-034339
    OpenUrlCrossRefPubMed
  6. ↵
    1. Lavin Y,
    2. Winter D,
    3. Blecher-Gonen R,
    4. David E,
    5. Keren-Shaul H,
    6. Merad M,
    7. Jung S,
    8. Amit I
    : Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159: 1312–1326, 2014 https://doi.org/10.1016/j.cell.2014.11.018
    OpenUrlCrossRefPubMed
  7. ↵
    1. George JF,
    2. Lever JM,
    3. Agarwal A
    : Mononuclear phagocyte subpopulations in the mouse kidney. Am J Physiol Renal Physiol 312: F640–F646, 2017 https://doi.org/10.1152/ajprenal.00369.2016
    OpenUrlCrossRefPubMed
  8. ↵
    1. Merad M,
    2. Sathe P,
    3. Helft J,
    4. Miller J,
    5. Mortha A
    : The dendritic cell lineage: Ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol 31: 563–604, 2013 https://doi.org/10.1146/annurev-immunol-020711-074950
    OpenUrlCrossRefPubMed
  9. ↵
    1. Geissmann F,
    2. Manz MG,
    3. Jung S,
    4. Sieweke MH,
    5. Merad M,
    6. Ley K
    : Development of monocytes, macrophages, and dendritic cells. Science 327: 656–661, 2010 https://doi.org/10.1126/science.1178331
    OpenUrlAbstract/FREE Full Text
  10. ↵
    1. Salei N,
    2. Rambichler S,
    3. Salvermoser J,
    4. Papaioannou NE,
    5. Schuchert R,
    6. Pakalniškytė D,
    7. Li N,
    8. Marschner JA,
    9. Lichtnekert J,
    10. Stremmel C,
    11. Cernilogar FM,
    12. Salvermoser M,
    13. Walzog B,
    14. Straub T,
    15. Schotta G,
    16. Anders HJ,
    17. Schulz C,
    18. Schraml BU
    : The kidney contains ontogenetically distinct dendritic cell and macrophage subtypes throughout development that differ in their inflammatory properties. J Am Soc Nephrol 31: 257–278, 2020 https://doi.org/10.1681/ASN.2019040419
    OpenUrlAbstract/FREE Full Text
  11. ↵
    1. Zimmerman KA,
    2. Bentley MR,
    3. Lever JM,
    4. Li Z,
    5. Crossman DK,
    6. Song CJ,
    7. Liu S,
    8. Crowley MR,
    9. George JF,
    10. Mrug M,
    11. Yoder BK
    : Single-cell RNA sequencing identifies candidate renal resident macrophage gene expression signatures across species. J Am Soc Nephrol 30: 767–781, 2019 https://doi.org/10.1681/ASN.2018090931
    OpenUrlAbstract/FREE Full Text
  12. ↵
    1. Schulz C,
    2. Gomez Perdiguero E,
    3. Chorro L,
    4. Szabo-Rogers H,
    5. Cagnard N,
    6. Kierdorf K,
    7. Prinz M,
    8. Wu B,
    9. Jacobsen SE,
    10. Pollard JW,
    11. Frampton J,
    12. Liu KJ,
    13. Geissmann F
    : A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336: 86–90, 2012 https://doi.org/10.1126/science.1219179
    OpenUrlAbstract/FREE Full Text
  13. ↵
    1. Hoeffel G,
    2. Chen J,
    3. Lavin Y,
    4. Low D,
    5. Almeida FF,
    6. See P,
    7. Beaudin AE,
    8. Lum J,
    9. Low I,
    10. Forsberg EC,
    11. Poidinger M,
    12. Zolezzi F,
    13. Larbi A,
    14. Ng LG,
    15. Chan JK,
    16. Greter M,
    17. Becher B,
    18. Samokhvalov IM,
    19. Merad M,
    20. Ginhoux F
    : C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages. Immunity 42: 665–678, 2015 https://doi.org/10.1016/j.immuni.2015.03.011
    OpenUrlCrossRefPubMed
  14. ↵
    1. Hoeffel G,
    2. Ginhoux F
    : Ontogeny of tissue-resident macrophages. Front Immunol 6: 486, 2015 https://doi.org/10.3389/fimmu.2015.00486
    OpenUrlCrossRefPubMed
  15. ↵
    1. Jang HS,
    2. Kim JI,
    3. Jung KJ,
    4. Kim J,
    5. Han KH,
    6. Park KM
    : Bone marrow-derived cells play a major role in kidney fibrosis via proliferation and differentiation in the infiltrated site. Biochim Biophys Acta 1832: 817–825, 2013 https://doi.org/10.1016/j.bbadis.2013.02.016
    OpenUrl
  16. ↵
    1. Sheng J,
    2. Ruedl C,
    3. Karjalainen K
    : Most tissue-resident macrophages except microglia are derived from fetal hematopoietic stem cells. Immunity 43: 382–393, 2015 https://doi.org/10.1016/j.immuni.2015.07.016
    OpenUrlCrossRefPubMed
  17. ↵
    1. Munro DAD,
    2. Hughes J
    : The origins and functions of tissue-resident macrophages in kidney development. Front Physiol 8: 837, 2017 https://doi.org/10.3389/fphys.2017.00837
    OpenUrlPubMed
  18. ↵
    1. Liu F,
    2. Dai S,
    3. Feng D,
    4. Qin Z,
    5. Peng X,
    6. Sakamuri SSVP,
    7. Ren M,
    8. Huang L,
    9. Cheng M,
    10. Mohammad KE,
    11. Qu P,
    12. Chen Y,
    13. Zhao C,
    14. Zhu F,
    15. Liang S,
    16. Aktas BH,
    17. Yang X,
    18. Wang H,
    19. Katakam PVG,
    20. Busija DW,
    21. Fischer T,
    22. Datta PK,
    23. Rappaport J,
    24. Gao B,
    25. Qin X
    : Distinct fate, dynamics and niches of renal macrophages of bone marrow or embryonic origins. Nat Commun 11: 2280, 2020 https://doi.org/10.1038/s41467-020-16158-z
    OpenUrl
  19. ↵
    1. Liu Z,
    2. Gu Y,
    3. Chakarov S,
    4. Bleriot C,
    5. Kwok I,
    6. Chen X,
    7. Shin A,
    8. Huang W,
    9. Dress RJ,
    10. Dutertre CA,
    11. Schlitzer A,
    12. Chen J,
    13. Ng LG,
    14. Wang H,
    15. Liu Z,
    16. Su B,
    17. Ginhoux F
    : Fate mapping via ms4a3-expression history traces monocyte-derived cells. Cell 178: 1509–1525.e19, 2019 https://doi.org/10.1016/j.cell.2019.08.009
    OpenUrlCrossRefPubMed
  20. ↵
    1. Zimmerman KA,
    2. Song CJ,
    3. Li Z,
    4. Lever JM,
    5. Crossman DK,
    6. Rains A,
    7. Aloria EJ,
    8. Gonzalez NM,
    9. Bassler JR,
    10. Zhou J,
    11. Crowley MR,
    12. Revell DZ,
    13. Yan Z,
    14. Shan D,
    15. Benveniste EN,
    16. George JF,
    17. Mrug M,
    18. Yoder BK
    : Tissue-resident macrophages promote renal cystic disease. J Am Soc Nephrol 30: 1841–1856, 2019 https://doi.org/10.1681/ASN.2018080810
    OpenUrlAbstract/FREE Full Text
  21. ↵
    1. Lever JM,
    2. Hull TD,
    3. Boddu R,
    4. Pepin ME,
    5. Black LM,
    6. Adedoyin OO,
    7. Yang Z,
    8. Traylor AM,
    9. Jiang Y,
    10. Li Z,
    11. Peabody JE,
    12. Eckenrode HE,
    13. Crossman DK,
    14. Crowley MR,
    15. Bolisetty S,
    16. Zimmerman KA,
    17. Wende AR,
    18. Mrug M,
    19. Yoder BK,
    20. Agarwal A,
    21. George JF
    : Resident macrophages reprogram toward a developmental state after acute kidney injury. JCI Insight 4: e125503, 2019 https://doi.org/10.1172/jci.insight.125503
    OpenUrl
  22. ↵
    1. Stamatiades EG,
    2. Tremblay ME,
    3. Bohm M,
    4. Crozet L,
    5. Bisht K,
    6. Kao D,
    7. Coelho C,
    8. Fan X,
    9. Yewdell WT,
    10. Davidson A,
    11. Heeger PS,
    12. Diebold S,
    13. Nimmerjahn F,
    14. Geissmann F
    : Immune monitoring of trans-endothelial transport by kidney-resident macrophages. Cell 166: 991–1003, 2016 https://doi.org/10.1016/j.cell.2016.06.058
    OpenUrlCrossRefPubMed
  23. ↵
    1. Munro DAD,
    2. Wineberg Y,
    3. Tarnick J,
    4. Vink CS,
    5. Li Z,
    6. Pridans C,
    7. Dzierzak E,
    8. Kalisky T,
    9. Hohenstein P,
    10. Davies JA
    : Macrophages restrict the nephrogenic field and promote endothelial connections during kidney development. eLife 8: e43271, 2019 https://doi.org/10.7554/eLife.43271
    OpenUrl
  24. ↵
    1. Uderhardt S,
    2. Martins AJ,
    3. Tsang JS,
    4. Lämmermann T,
    5. Germain RN
    : Resident macrophages cloak tissue microlesions to prevent neutrophil-driven inflammatory damage. Cell 177: 541–555.e17, 2019 https://doi.org/10.1016/j.cell.2019.02.028
    OpenUrlCrossRefPubMed
  25. ↵
    1. Rőszer T
    : Understanding the mysterious M2 macrophage through activation markers and effector mechanisms. Mediators Inflamm 2015: 816460, 2015 https://doi.org/10.1155/2015/816460
    OpenUrlPubMed
  26. ↵
    1. Yang Y,
    2. Chen M,
    3. Zhou J,
    4. Lv J,
    5. Song S,
    6. Fu L,
    7. Chen J,
    8. Yang M,
    9. Mei C
    : Interactions between macrophages and cyst-lining epithelial cells promote kidney cyst growth in Pkd1-deficient mice. J Am Soc Nephrol 29: 2310–2325, 2018 https://doi.org/10.1681/ASN.2018010074
    OpenUrlAbstract/FREE Full Text
  27. ↵
    1. Lin SL,
    2. Li B,
    3. Rao S,
    4. Yeo EJ,
    5. Hudson TE,
    6. Nowlin BT,
    7. Pei H,
    8. Chen L,
    9. Zheng JJ,
    10. Carroll TJ,
    11. Pollard JW,
    12. McMahon AP,
    13. Lang RA,
    14. Duffield JS
    : Macrophage Wnt7b is critical for kidney repair and regeneration. Proc Natl Acad Sci U S A 107: 4194–4199, 2010 https://doi.org/10.1073/pnas.0912228107
    OpenUrlAbstract/FREE Full Text
  28. ↵
    1. Cao Q,
    2. Harris DC,
    3. Wang Y
    : Macrophages in kidney injury, inflammation, and fibrosis. Physiology (Bethesda) 30: 183–194, 2015 https://doi.org/10.1152/physiol.00046.2014
    OpenUrlCrossRefPubMed
  29. ↵
    1. Ferenbach DA,
    2. Sheldrake TA,
    3. Dhaliwal K,
    4. Kipari TM,
    5. Marson LP,
    6. Kluth DC,
    7. Hughes J
    : Macrophage/monocyte depletion by clodronate, but not diphtheria toxin, improves renal ischemia/reperfusion injury in mice. Kidney Int 82: 928–933, 2012 https://doi.org/10.1038/ki.2012.207
    OpenUrlCrossRefPubMed
  30. ↵
    1. Cowley BD Jr.,
    2. Gudapaty S,
    3. Kraybill AL,
    4. Barash BD,
    5. Harding MA,
    6. Calvet JP,
    7. Gattone VH 2nd.
    : Autosomal-dominant polycystic kidney disease in the rat. Kidney Int 43: 522–534, 1993 https://doi.org/10.1038/ki.1993.79
    OpenUrlCrossRefPubMed
  31. ↵
    1. Vogler C,
    2. Homan S,
    3. Pung A,
    4. Thorpe C,
    5. Barker J,
    6. Birkenmeier EH,
    7. Upadhya P
    : Clinical and pathologic findings in two new allelic murine models of polycystic kidney disease. J Am Soc Nephrol 10: 2534–2539, 1999
    OpenUrlAbstract/FREE Full Text
  32. ↵
    1. Cowley BD Jr.,
    2. Ricardo SD,
    3. Nagao S,
    4. Diamond JR
    : Increased renal expression of monocyte chemoattractant protein-1 and osteopontin in ADPKD in rats. Kidney Int 60: 2087–2096, 2001 https://doi.org/10.1046/j.1523-1755.2001.00065.x
    OpenUrlCrossRefPubMed
  33. ↵
    1. Phillips JK,
    2. Hopwood D,
    3. Loxley RA,
    4. Ghatora K,
    5. Coombes JD,
    6. Tan YS,
    7. Harrison JL,
    8. McKitrick DJ,
    9. Holobotvskyy V,
    10. Arnolda LF,
    11. Rangan GK
    : Temporal relationship between renal cyst development, hypertension and cardiac hypertrophy in a new rat model of autosomal recessive polycystic kidney disease. Kidney Blood Press Res 30: 129–144, 2007 https://doi.org/10.1159/000101828
    OpenUrlCrossRefPubMed
  34. ↵
    1. Karihaloo A,
    2. Koraishy F,
    3. Huen SC,
    4. Lee Y,
    5. Merrick D,
    6. Caplan MJ,
    7. Somlo S,
    8. Cantley LG
    : Macrophages promote cyst growth in polycystic kidney disease. J Am Soc Nephrol 22: 1809–1814, 2011 https://doi.org/10.1681/ASN.2011010084
    OpenUrlAbstract/FREE Full Text
  35. ↵
    1. Swenson-Fields KI,
    2. Vivian CJ,
    3. Salah SM,
    4. Peda JD,
    5. Davis BM,
    6. van Rooijen N,
    7. Wallace DP,
    8. Fields TA
    : Macrophages promote polycystic kidney disease progression. Kidney Int 83: 855–864, 2013 https://doi.org/10.1038/ki.2012.446
    OpenUrlCrossRefPubMed
  36. ↵
    1. Viau A,
    2. Bienaimé F,
    3. Lukas K,
    4. Todkar AP,
    5. Knoll M,
    6. Yakulov TA,
    7. Hofherr A,
    8. Kretz O,
    9. Helmstädter M,
    10. Reichardt W,
    11. Braeg S,
    12. Aschman T,
    13. Merkle A,
    14. Pfeifer D,
    15. Dumit VI,
    16. Gubler MC,
    17. Nitschke R,
    18. Huber TB,
    19. Terzi F,
    20. Dengjel J,
    21. Grahammer F,
    22. Köttgen M,
    23. Busch H,
    24. Boerries M,
    25. Walz G,
    26. Triantafyllopoulou A,
    27. Kuehn EW
    : Cilia-localized LKB1 regulates chemokine signaling, macrophage recruitment, and tissue homeostasis in the kidney. EMBO J 37: e98615, 2018 https://doi.org/10.15252/embj.201798615
    OpenUrlAbstract/FREE Full Text
  37. ↵
    1. Cassini MF,
    2. Kakade VR,
    3. Kurtz E,
    4. Sulkowski P,
    5. Glazer P,
    6. Torres R,
    7. Somlo S,
    8. Cantley LG
    : Mcp1 promotes macrophage-dependent cyst expansion in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 29: 2471–2481, 2018 https://doi.org/10.1681/ASN.2018050518
    OpenUrlAbstract/FREE Full Text
  38. ↵
    1. Chen L,
    2. Zhou X,
    3. Fan LX,
    4. Yao Y,
    5. Swenson-Fields KI,
    6. Gadjeva M,
    7. Wallace DP,
    8. Peters DJ,
    9. Yu A,
    10. Grantham JJ,
    11. Li X
    : Macrophage migration inhibitory factor promotes cyst growth in polycystic kidney disease. J Clin Invest 125: 2399–2412, 2015 https://doi.org/10.1172/JCI80467
    OpenUrlCrossRefPubMed
  39. ↵
    1. Kim HJ,
    2. Edelstein CL
    : Mammalian target of rapamycin inhibition in polycystic kidney disease: From bench to bedside. Kidney Res Clin Pract 31: 132–138, 2012 https://doi.org/10.1016/j.krcp.2012.07.002
    OpenUrl
  40. ↵
    1. Torres VE
    : Vasopressin antagonists in polycystic kidney disease. Semin Nephrol 28: 306–317, 2008 https://doi.org/10.1016/j.semnephrol.2008.03.003
    OpenUrlCrossRefPubMed
  41. ↵
    1. Zimmerman KA,
    2. Song CJ,
    3. Gonzalez-Mize N,
    4. Li Z,
    5. Yoder BK
    : Primary cilia disruption differentially affects the infiltrating and resident macrophage compartment in the liver. Am J Physiol Gastrointest Liver Physiol 314: G677–G689, 2018 https://doi.org/10.1152/ajpgi.00381.2017
    OpenUrlCrossRefPubMed
  42. ↵
    1. Zoja C,
    2. Corna D,
    3. Locatelli M,
    4. Rottoli D,
    5. Pezzotta A,
    6. Morigi M,
    7. Zanchi C,
    8. Buelli S,
    9. Guglielmotti A,
    10. Perico N,
    11. Remuzzi A,
    12. Remuzzi G
    : Effects of MCP-1 inhibition by bindarit therapy in a rat model of polycystic kidney disease. Nephron 129: 52–61, 2015 https://doi.org/10.1159/000369149
    OpenUrlCrossRefPubMed
  43. ↵
    1. Salah SM,
    2. Meisenheimer JD,
    3. Rao R,
    4. Peda JD,
    5. Wallace DP,
    6. Foster D,
    7. Li X,
    8. Li X,
    9. Zhou X,
    10. Vallejo JA,
    11. Wacker MJ,
    12. Fields TA,
    13. Swenson-Fields KI
    : MCP-1 promotes detrimental cardiac physiology, pulmonary edema, and death in the cpk model of polycystic kidney disease. Am J Physiol Renal Physiol 317: F343–F360, 2019 https://doi.org/10.1152/ajprenal.00240.2018
    OpenUrl
  44. ↵
    1. Li X
    1. Karihaloo A
    : Role of inflammation in polycystic kidney disease. In: Polycystic Kidney Disease, edited by Li X, Brisbane (AU), Codon Publications, 2015 https://doi.org/10.15586/codon.pkd.2015.ch14
  45. ↵
    1. Ta MH,
    2. Harris DC,
    3. Rangan GK
    : Role of interstitial inflammation in the pathogenesis of polycystic kidney disease. Nephrology (Carlton) 18: 317–330, 2013 https://doi.org/10.1111/nep.12045
    OpenUrlCrossRefPubMed
  46. ↵
    1. Song CJ,
    2. Zimmerman KA,
    3. Henke SJ,
    4. Yoder BK
    : Inflammation and fibrosis in polycystic kidney disease. Results Probl Cell Differ 60: 323–344, 2017 https://doi.org/10.1007/978-3-319-51436-9_12
    OpenUrlCrossRefPubMed
  47. ↵
    1. Zimmerman KA,
    2. Hopp K,
    3. Mrug M
    : Role of chemokines, innate and adaptive immunity. Cell Signal 73: 109647, 2020 https://doi.org/10.1016/j.cellsig.2020.109647
    OpenUrl
  48. ↵
    1. Lakhia R,
    2. Yheskel M,
    3. Flaten A,
    4. Ramalingam H,
    5. Aboudehen K,
    6. Ferrè S,
    7. Biggers L,
    8. Mishra A,
    9. Chaney C,
    10. Wallace DP,
    11. Carroll T,
    12. Igarashi P,
    13. Patel V
    : Interstitial microRNA miR-214 attenuates inflammation and polycystic kidney disease progression. JCI Insight 5: e133785, 2020 https://doi.org/10.1172/jci.insight.133785
    OpenUrl
  49. ↵
    1. Stewart BJ,
    2. Ferdinand JR,
    3. Young MD,
    4. Mitchell TJ,
    5. Loudon KW,
    6. Riding AM,
    7. Richoz N,
    8. Frazer GL,
    9. Staniforth JUL,
    10. Vieira Braga FA,
    11. Botting RA,
    12. Popescu DM,
    13. Vento-Tormo R,
    14. Stephenson E,
    15. Cagan A,
    16. Farndon SJ,
    17. Polanski K,
    18. Efremova M,
    19. Green K,
    20. Del Castillo Velasco-Herrera M,
    21. Guzzo C,
    22. Collord G,
    23. Mamanova L,
    24. Aho T,
    25. Armitage JN,
    26. Riddick ACP,
    27. Mushtaq I,
    28. Farrell S,
    29. Rampling D,
    30. Nicholson J,
    31. Filby A,
    32. Burge J,
    33. Lisgo S,
    34. Lindsay S,
    35. Bajenoff M,
    36. Warren AY,
    37. Stewart GD,
    38. Sebire N,
    39. Coleman N,
    40. Haniffa M,
    41. Teichmann SA,
    42. Behjati S,
    43. Clatworthy MR
    : Spatiotemporal immune zonation of the human kidney. Science 365: 1461–1466, 2019 https://doi.org/10.1126/science.aat5031
    OpenUrlAbstract/FREE Full Text
  50. ↵
    1. Mrug M,
    2. Zhou J,
    3. Woo Y,
    4. Cui X,
    5. Szalai AJ,
    6. Novak J,
    7. Churchill GA,
    8. Guay-Woodford LM
    : Overexpression of innate immune response genes in a model of recessive polycystic kidney disease. Kidney Int 73: 63–76, 2008 https://doi.org/10.1038/sj.ki.5002627
    OpenUrlCrossRefPubMed
  51. ↵
    1. Sharma N,
    2. Malarkey EB,
    3. Berbari NF,
    4. O’Connor AK,
    5. Vanden Heuvel GB,
    6. Mrug M,
    7. Yoder BK
    : Proximal tubule proliferation is insufficient to induce rapid cyst formation after cilia disruption. J Am Soc Nephrol 24: 456–464, 2013 https://doi.org/10.1681/ASN.2012020154
    OpenUrlAbstract/FREE Full Text
  52. ↵
    1. Conway JG,
    2. McDonald B,
    3. Parham J,
    4. Keith B,
    5. Rusnak DW,
    6. Shaw E,
    7. Jansen M,
    8. Lin P,
    9. Payne A,
    10. Crosby RM,
    11. Johnson JH,
    12. Frick L,
    13. Lin MH,
    14. Depee S,
    15. Tadepalli S,
    16. Votta B,
    17. James I,
    18. Fuller K,
    19. Chambers TJ,
    20. Kull FC,
    21. Chamberlain SD,
    22. Hutchins JT
    : Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580. Proc Natl Acad Sci U S A 102: 16078–16083, 2005 https://doi.org/10.1073/pnas.0502000102
    OpenUrlAbstract/FREE Full Text
  53. ↵
    1. Zimmerman KA,
    2. Huang J,
    3. He L,
    4. Revell DZ,
    5. Li Z,
    6. Hsu J-S,
    7. Fitzgibbon WR,
    8. Hazard ES,
    9. Hardiman G,
    10. Mrug M,
    11. Bell PD,
    12. Yoder BK,
    13. Saigusa T
    : Interferon regulatory factor‐5 in resident macrophage promotes polycystic kidney disease. Kidney360 1: 179–190, 2020 https://doi.org/10.34067/KID.0001052019
    OpenUrlAbstract/FREE Full Text
  54. ↵
    1. Weiss M,
    2. Blazek K,
    3. Byrne AJ,
    4. Perocheau DP,
    5. Udalova IA
    : IRF5 is a specific marker of inflammatory macrophages in vivo. Mediators Inflamm 2013: 245804, 2013 https://doi.org/10.1155/2013/245804
    OpenUrlPubMed
  55. ↵
    1. Harris PC,
    2. Torres VE
    : Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney disease. J Clin Invest 124: 2315–2324, 2014 https://doi.org/10.1172/JCI72272
    OpenUrlCrossRefPubMed
  56. ↵
    1. Zhou D,
    2. Tan RJ,
    3. Fu H,
    4. Liu Y
    : Wnt/β-catenin signaling in kidney injury and repair: A double-edged sword. Lab Invest 96: 156–167, 2016 https://doi.org/10.1038/labinvest.2015.153
    OpenUrlCrossRefPubMed
  57. ↵
    1. Whyte JL,
    2. Smith AA,
    3. Helms JA
    : Wnt signaling and injury repair. Cold Spring Harb Perspect Biol 4: a008078, 2012 https://doi.org/10.1101/cshperspect.a008078
    OpenUrlAbstract/FREE Full Text
  58. ↵
    1. Maarouf OH,
    2. Aravamudhan A,
    3. Rangarajan D,
    4. Kusaba T,
    5. Zhang V,
    6. Welborn J,
    7. Gauvin D,
    8. Hou X,
    9. Kramann R,
    10. Humphreys BD
    : Paracrine Wnt1 drives interstitial fibrosis without inflammation by tubulointerstitial cross-talk. J Am Soc Nephrol 27: 781–790, 2016 https://doi.org/10.1681/ASN.2014121188
    OpenUrlAbstract/FREE Full Text
  59. ↵
    1. Prasad S,
    2. McDaid JP,
    3. Tam FW,
    4. Haylor JL,
    5. Ong AC
    : Pkd2 dosage influences cellular repair responses following ischemia-reperfusion injury. Am J Pathol 175: 1493–1503, 2009 https://doi.org/10.2353/ajpath.2009.090227
    OpenUrlCrossRefPubMed
  60. ↵
    1. Bernhardt WM,
    2. Wiesener MS,
    3. Weidemann A,
    4. Schmitt R,
    5. Weichert W,
    6. Lechler P,
    7. Campean V,
    8. Ong AC,
    9. Willam C,
    10. Gretz N,
    11. Eckardt KU
    : Involvement of hypoxia-inducible transcription factors in polycystic kidney disease. Am J Pathol 170: 830–842, 2007 https://doi.org/10.2353/ajpath.2007.060455
    OpenUrlCrossRefPubMed
  61. ↵
    1. Kleczko EK,
    2. Marsh KH,
    3. Tyler LC,
    4. Furgeson SB,
    5. Bullock BL,
    6. Altmann CJ,
    7. Miyazaki M,
    8. Gitomer BY,
    9. Harris PC,
    10. Weiser-Evans MCM,
    11. Chonchol MB,
    12. Clambey ET,
    13. Nemenoff RA,
    14. Hopp K
    : CD8+ T cells modulate autosomal dominant polycystic kidney disease progression. Kidney Int 94: 1127–1140, 2018 https://doi.org/10.1016/j.kint.2018.06.025
    OpenUrlPubMed
  62. ↵
    1. Zimmerman KA,
    2. Gonzalez NM,
    3. Chumley P,
    4. Chacana T,
    5. Harrington LE,
    6. Yoder BK,
    7. Mrug M
    : Urinary T cells correlate with rate of renal function loss in autosomal dominant polycystic kidney disease. Physiol Rep 7: e13951, 2019 https://doi.org/10.14814/phy2.13951
    OpenUrlPubMed
  63. ↵
    1. Franken L,
    2. Schiwon M,
    3. Kurts C
    : Macrophages: Sentinels and regulators of the immune system. Cell Microbiol 18: 475–487, 2016 https://doi.org/10.1111/cmi.12580
    OpenUrlCrossRef
  64. ↵
    1. Li X
    1. Zhou JX,
    2. Li X
    : Apoptosis in polycystic kidney disease: From pathogenesis to treatment. In: Polycystic Kidney Disease, edited by Li X, Brisbane (AU), Codon Publications, 2015
  65. ↵
    1. Roberts AW,
    2. Lee BL,
    3. Deguine J,
    4. John S,
    5. Shlomchik MJ,
    6. Barton GM
    : Tissue-resident macrophages are locally programmed for silent clearance of apoptotic cells. Immunity 47: 913–927.e6, 2017 https://doi.org/10.1016/j.immuni.2017.10.006
    OpenUrl
  66. ↵
    1. Puranik AS,
    2. Leaf IA,
    3. Jensen MA,
    4. Hedayat AF,
    5. Saad A,
    6. Kim KW,
    7. Saadalla AM,
    8. Woollard JR,
    9. Kashyap S,
    10. Textor SC,
    11. Grande JP,
    12. Lerman A,
    13. Simari RD,
    14. Randolph GJ,
    15. Duffield JS,
    16. Lerman LO
    : Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney. Sci Rep 8: 13948, 2018 https://doi.org/10.1038/s41598-018-31887-4
    OpenUrlCrossRefPubMed
  67. ↵
    1. Karasawa K,
    2. Asano K,
    3. Moriyama S,
    4. Ushiki M,
    5. Monya M,
    6. Iida M,
    7. Kuboki E,
    8. Yagita H,
    9. Uchida K,
    10. Nitta K,
    11. Tanaka M
    : Vascular-resident CD169-positive monocytes and macrophages control neutrophil accumulation in the kidney with ischemia-reperfusion injury. J Am Soc Nephrol 26: 896–906, 2015 https://doi.org/10.1681/ASN.2014020195
    OpenUrlAbstract/FREE Full Text
  68. ↵
    1. Norlander AE,
    2. Madhur MS
    : Inflammatory cytokines regulate renal sodium transporters: How, where, and why? Am J Physiol Renal Physiol 313: F141–F144, 2017 https://doi.org/10.1152/ajprenal.00465.2016
    OpenUrlCrossRefPubMed
  69. ↵
    1. Zhang J,
    2. Rudemiller NP,
    3. Patel MB,
    4. Karlovich NS,
    5. Wu M,
    6. McDonough AA,
    7. Griffiths R,
    8. Sparks MA,
    9. Jeffs AD,
    10. Crowley SD
    : Interleukin-1 receptor activation potentiates salt reabsorption in angiotensin II-induced hypertension via the NKCC2 Co-transporter in the nephron. Cell Metab 23: 360–368, 2016 https://doi.org/10.1016/j.cmet.2015.11.013
    OpenUrlCrossRefPubMed
  70. ↵
    1. Veit G,
    2. Bossard F,
    3. Goepp J,
    4. Verkman AS,
    5. Galietta LJ,
    6. Hanrahan JW,
    7. Lukacs GL
    : Proinflammatory cytokine secretion is suppressed by TMEM16A or CFTR channel activity in human cystic fibrosis bronchial epithelia. Mol Biol Cell 23: 4188–4202, 2012 https://doi.org/10.1091/mbc.e12-06-0424
    OpenUrlAbstract/FREE Full Text
  71. ↵
    1. Peteranderl C,
    2. Morales-Nebreda L,
    3. Selvakumar B,
    4. Lecuona E,
    5. Vadász I,
    6. Morty RE,
    7. Schmoldt C,
    8. Bespalowa J,
    9. Wolff T,
    10. Pleschka S,
    11. Mayer K,
    12. Gattenloehner S,
    13. Fink L,
    14. Lohmeyer J,
    15. Seeger W,
    16. Sznajder JI,
    17. Mutlu GM,
    18. Budinger GR,
    19. Herold S
    : Macrophage-epithelial paracrine crosstalk inhibits lung edema clearance during influenza infection. J Clin Invest 126: 1566–1580, 2016 https://doi.org/10.1172/JCI83931
    OpenUrlCrossRefPubMed
  72. ↵
    1. Huang JL,
    2. Woolf AS,
    3. Kolatsi-Joannou M,
    4. Baluk P,
    5. Sandford RN,
    6. Peters DJ,
    7. McDonald DM,
    8. Price KL,
    9. Winyard PJ,
    10. Long DA
    : Vascular endothelial growth factor C for polycystic kidney diseases. J Am Soc Nephrol 27: 69–77, 2016 https://doi.org/10.1681/ASN.2014090856
    OpenUrlAbstract/FREE Full Text
  73. ↵
    1. Jafree DJ,
    2. Moulding D,
    3. Kolatsi-Joannou M,
    4. Perretta Tejedor N,
    5. Price KL,
    6. Milmoe NJ,
    7. Walsh CL,
    8. Correra RM,
    9. Winyard PJ,
    10. Harris PC,
    11. Ruhrberg C,
    12. Walker-Samuel S,
    13. Riley PR,
    14. Woolf AS,
    15. Scambler PJ,
    16. Long DA
    : Spatiotemporal dynamics and heterogeneity of renal lymphatics in mammalian development and cystic kidney disease. eLife 8: e48183, 2019 https://doi.org/10.7554/eLife.48183
    OpenUrlPubMed
  74. ↵
    1. Takakura A,
    2. Nelson EA,
    3. Haque N,
    4. Humphreys BD,
    5. Zandi-Nejad K,
    6. Frank DA,
    7. Zhou J
    : Pyrimethamine inhibits adult polycystic kidney disease by modulating STAT signaling pathways. Hum Mol Genet 20: 4143–4154, 2011 https://doi.org/10.1093/hmg/ddr338
    OpenUrlCrossRefPubMed
  75. ↵
    1. Leuenroth SJ,
    2. Crews CM
    : Studies on calcium dependence reveal multiple modes of action for triptolide. Chem Biol 12: 1259–1268, 2005 https://doi.org/10.1016/j.chembiol.2005.09.009
    OpenUrlCrossRefPubMed
  76. ↵
    1. Leuenroth SJ,
    2. Bencivenga N,
    3. Igarashi P,
    4. Somlo S,
    5. Crews CM
    : Triptolide reduces cystogenesis in a model of ADPKD. J Am Soc Nephrol 19: 1659–1662, 2008 https://doi.org/10.1681/ASN.2008030259
    OpenUrlAbstract/FREE Full Text
  77. ↵
    1. Ponzoni M,
    2. Pastorino F,
    3. Di Paolo D,
    4. Perri P,
    5. Brignole C
    : Targeting macrophages as a potential therapeutic intervention: Impact on inflammatory diseases and cancer. Int J Mol Sci 19: 1953, 2018 https://doi.org/10.3390/ijms19071953
    OpenUrl
  78. ↵
    1. Paolicelli RC,
    2. Bolasco G,
    3. Pagani F,
    4. Maggi L,
    5. Scianni M,
    6. Panzanelli P,
    7. Giustetto M,
    8. Ferreira TA,
    9. Guiducci E,
    10. Dumas L,
    11. Ragozzino D,
    12. Gross CT
    : Synaptic pruning by microglia is necessary for normal brain development. Science 333: 1456–1458, 2011 https://doi.org/10.1126/science.1202529
    OpenUrlAbstract/FREE Full Text
  79. ↵
    1. Hulsmans M,
    2. Clauss S,
    3. Xiao L,
    4. Aguirre AD,
    5. King KR,
    6. Hanley A,
    7. Hucker WJ,
    8. Wülfers EM,
    9. Seemann G,
    10. Courties G,
    11. Iwamoto Y,
    12. Sun Y,
    13. Savol AJ,
    14. Sager HB,
    15. Lavine KJ,
    16. Fishbein GA,
    17. Capen DE,
    18. Da Silva N,
    19. Miquerol L,
    20. Wakimoto H,
    21. Seidman CE,
    22. Seidman JG,
    23. Sadreyev RI,
    24. Naxerova K,
    25. Mitchell RN,
    26. Brown D,
    27. Libby P,
    28. Weissleder R,
    29. Swirski FK,
    30. Kohl P,
    31. Vinegoni C,
    32. Milan DJ,
    33. Ellinor PT,
    34. Nahrendorf M
    : Macrophages facilitate electrical conduction in the heart. Cell 169: 510–522.e20, 2017 https://doi.org/10.1016/j.cell.2017.03.050
    OpenUrlCrossRefPubMed
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Resident Macrophages in Cystic Kidney Disease
Zhang Li, Kurt A. Zimmerman, Bradley K. Yoder
Kidney360 Jan 2021, 2 (1) 167-175; DOI: 10.34067/KID.0006052020
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