Resident Renal Mononuclear Phagocytes Comprise Five Discrete Populations with Distinct Phenotypes and Functions (original) (raw)

Journal Article

Takahisa Kawakami ,

Division of Nephrology, University of Washington

, Seattle, WA 98109

Institute of Stem Cell and Regenerative Medicine, University of Washington

, Seattle, WA 98109

Center for Lung Biology, University of Washington

, Seattle, WA 98109

Kidney Research Institute, University of Washington

, Seattle, WA 98109

Address correspondence and reprint requests to Dr. Takahisa Kawakami, Division of Nephrology, University of Washington, S371, Box 358052, 850 Republican Street, Seattle, WA 98109 (T.K.). E-mail address: [email protected] (T.K.)

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Julia Lichtnekert ,

Division of Nephrology, University of Washington

, Seattle, WA 98109

Institute of Stem Cell and Regenerative Medicine, University of Washington

, Seattle, WA 98109

Center for Lung Biology, University of Washington

, Seattle, WA 98109

Kidney Research Institute, University of Washington

, Seattle, WA 98109

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Lucas J Thompson ,

Benaroya Research Institute

, Seattle, WA 98101

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Prasanthi Karna ,

Division of Nephrology, University of Washington

, Seattle, WA 98109

Kidney Research Institute, University of Washington

, Seattle, WA 98109

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Hicham Bouabe ,

Lymphocyte Signaling and Development Institute Strategic Programmes, Babraham Institute

, Babraham, Cambridgeshire CB22 3AT,

United Kingdom

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Tobias M Hohl ,

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center

, Seattle, WA 98109

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Jay W Heinecke ,

Diabetes and Obesity Center of Excellence, University of Washington

, Seattle, WA 98109

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Steven F Ziegler ,

Benaroya Research Institute

, Seattle, WA 98101

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Peter J Nelson ,

Division of Nephrology, University of Washington

, Seattle, WA 98109

Kidney Research Institute, University of Washington

, Seattle, WA 98109

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Jeremy S Duffield

Division of Nephrology, University of Washington

, Seattle, WA 98109

Institute of Stem Cell and Regenerative Medicine, University of Washington

, Seattle, WA 98109

Center for Lung Biology, University of Washington

, Seattle, WA 98109

Kidney Research Institute, University of Washington

, Seattle, WA 98109

Address correspondence and reprint requests to Prof. Jeremy S. Duffield, University of Washington School of Medicine, S371, Box 358052, 850 Republican Street, Seattle, WA 98109 (J.S.D.). E-mail address: [email protected] (J.S.D.)

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Received:

06 February 2013

Published:

15 September 2013

Cite

Takahisa Kawakami, Julia Lichtnekert, Lucas J Thompson, Prasanthi Karna, Hicham Bouabe, Tobias M Hohl, Jay W Heinecke, Steven F Ziegler, Peter J Nelson, Jeremy S Duffield, Resident Renal Mononuclear Phagocytes Comprise Five Discrete Populations with Distinct Phenotypes and Functions, The Journal of Immunology, Volume 191, Issue 6, September 2013, Pages 3358–3372, https://doi.org/10.4049/jimmunol.1300342
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Abstract

Recent reports have highlighted greater complexity, plasticity, and functional diversity of mononuclear phagocytes (MPCs), including monocytes, macrophages, and dendritic cells (DCs), in our organs than previously understood. The functions and origins of MPCs resident within healthy organs, especially in the kidney, are less well understood, whereas studies suggest they play roles in disease states distinct from recruited monocytes. We developed an unbiased approach using flow cytometry to analyze MPCs residing in the normal mouse kidney, and identified five discrete subpopulations according to CD11b/CD11c expression as well as F4/80, CD103, CD14, CD16, and CD64 expression. In addition to distinct marker profiles, these subpopulations have different lineages and expression of genes involved in tissue homeostasis, including angiogenesis. Among them, the CD11bintCD11cint F4/80high subpopulation notably exhibited high capacity to produce a representative anti-inflammatory cytokine, IL-10. Each subpopulation had different degrees of both macrophage (phagocytosis) and DC (Ag presentation) capacities, with a tendency to promote differentiation of regulatory T cells, whereas two of these showed expression of transcription factors reported to be highly expressed by classical DCs, and proclivity to exit the kidney following stimulation with LPS. In summary, resident kidney MPCs comprise discrete subpopulations, which cannot be simply classified into the conventional entities, and they produce anti-inflammatory and tissue-homeostatic factors to differing degrees.

Copyright © 2013 by The American Association of Immunologists, Inc.

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