Resident renal mononuclear phagocytes comprise five discrete populations with distinct phenotypes and functions

Takahisa Kawakami1, Julia Lichtnekert, Lucas J Thompson

  • 1Division of Nephrology, University of Washington, Seattle, WA 98109, USA. kawakat-tky@umin.net

Insights

Resident kidney mononuclear phagocytes (MPCs) are more diverse than previously thought. These distinct MPC subpopulations in the kidney play varied roles in tissue homeostasis and immune responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Renal Science

Background:

  • Mononuclear phagocytes (MPCs), including monocytes, macrophages, and dendritic cells (DCs), exhibit complex functions in organs.
  • The specific roles and origins of MPCs in healthy kidneys are not well understood.
  • Resident kidney MPCs may have functions distinct from recruited monocytes during disease.

Purpose of the Study:

  • To characterize the heterogeneity of mononuclear phagocytes residing in the normal mouse kidney.
  • To identify distinct subpopulations of kidney-resident MPCs and their functional capacities.

Main Methods:

  • Utilized an unbiased flow cytometry approach to analyze MPCs in the normal mouse kidney.
  • Characterized subpopulations based on CD11b/CD11c, F4/80, CD103, CD14, CD16, and CD64 expression.
  • Assessed gene expression related to tissue homeostasis and functional capacities like cytokine production and antigen presentation.

Main Results:

  • Identified five discrete MPC subpopulations in the mouse kidney based on surface marker expression.
  • These subpopulations displayed distinct lineage markers and gene expression profiles related to tissue homeostasis and angiogenesis.
  • One subpopulation (CD11b(int)CD11c(int) F4/80(high)) showed high capacity for producing the anti-inflammatory cytokine IL-10.
  • Different subpopulations exhibited varying phagocytic (macrophage) and antigen-presenting (DC) capacities, influencing regulatory T cell differentiation.
  • Two subpopulations expressed transcription factors characteristic of classical DCs and could egress from the kidney upon LPS stimulation.

Conclusions:

  • Resident kidney MPCs are composed of diverse subpopulations that defy simple classification into conventional immune cell types.
  • These subpopulations contribute to kidney homeostasis by producing anti-inflammatory and tissue-protective factors.
  • The distinct functional profiles of kidney-resident MPCs suggest specialized roles in renal health and potentially disease.

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