Key Points
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Dendritic cells (DCs) and macrophages are distinct cell types, but demonstrate similarities in terms of ontogeny, phenotype, and function
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Both of these cell types are present within the renal interstitium and are critical to homeostatic regulation of the kidney environment
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The numbers of DCs and macrophages in the kidney increase following renal injury
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A variety of DC and macrophage subtypes exist, each with distinct phenotypes and activities, and many can be identified based on panels of cellular markers
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The manifestation of glomerular or tubular kidney disease, as well as disease outcome in preclinical models, is determined by the subtype of DC and/or macrophage involved
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A number of pharmacological or genetic approaches are available to deplete or eliminate DCs or macrophages in preclinical models, but the effects of such interventions are not renal-specific
Abstract
Renal dendritic cells (DCs) and macrophages represent a constitutive, extensive and contiguous network of innate immune cells that provide sentinel and immune-intelligence activity; they induce and regulate inflammatory responses to freely filtered antigenic material and protect the kidney from infection. Tissue-resident or infiltrating DCs and macrophages are key factors in the initiation and propagation of renal disease, as well as essential contributors to subsequent tissue regeneration, regardless of the aetiological and pathogenetic mechanisms. The identification, and functional and phenotypic distinction of these cell types is complex and incompletely understood, and the same is true of their interplay and relationships with effector and regulatory cells of the adaptive immune system. In this Review, we discuss the common and distinct characteristics of DCs and macrophages, as well as key advances that have identified the renal-specific functions of these important phagocytic, antigen-presenting cells, and their roles in potentiating or mitigating intrinsic kidney disease. We also identify remaining issues that are of priority for further investigation, and highlight the prospects for translational and therapeutic application of the knowledge acquired.
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Acknowledgements
The work of the authors is supported by the NIH grants R01HL108954 and R01HL112914 (J.S.I.), and R01AI67541 and U01AI51698 (A.W.T.); the University of Pittsburgh O'Brien Kidney Pilot Award (J.S.I.); the Cunningham Trust, the Mrs A. E. Hogg Charitable Trust, Kidney Research UK and the UK Medical Research Council (J.H.); an American Heart Association Postdoctoral Award (13POST14520003) and an American Society of Transplantation/Pfizer Basic Science Fellowship (N.M.R.); and a Wellcome Trust Intermediate fellowship (D.A.F.). The work of J.S.I. is also supported by the Institute for Transfusion Medicine, the Haemophilia Center of Western Pennsylvania, and the Vascular Medicine Institute.
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J.S.I. contributed substantially to discussion of content and reviewed/edited the manuscript before submission. All other authors made substantial contributions to all stages of the preparation of the manuscript for submission. A.W.T and J.H. contributed equally as senior co-authors.
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J.S.I. is Chair of the Scientific Advisory Boards of Radiation Control Technologies and Vasculox. A.W.T. is co-inventor of a US patent (6,224,859 B1) for the generation of tolerogenic dendritic cells to promote transplant tolerance. The other authors declare no competing interests.
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Rogers, N., Ferenbach, D., Isenberg, J. et al. Dendritic cells and macrophages in the kidney: a spectrum of good and evil. Nat Rev Nephrol 10, 625–643 (2014). https://doi.org/10.1038/nrneph.2014.170
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DOI: https://doi.org/10.1038/nrneph.2014.170
