Kidney resident macrophages in the rat have minimal turnover and replacement by blood monocytes

Kurt A Zimmerman1,2, Zhengqin Yang3, Jeremie M Lever3

  • 1Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama.

Insights

Kidney resident macrophages (KRMs) in rats are self-renewing and do not rely heavily on blood input for maintenance. This finding confirms a key characteristic of mouse KRMs is conserved across species.

Area of Science:

  • Immunology
  • Renal Biology
  • Cell Biology

Background:

  • Kidney resident macrophages (KRMs) are crucial for kidney homeostasis and disease outcomes.
  • In mice, KRMs self-renew with minimal peripheral blood contribution.
  • Similar KRM-like cells exist across species, but their self-renewal capacity in non-rodent models is unproven.

Purpose of the Study:

  • To investigate if rat KRMs are maintained independently of peripheral blood input.
  • To determine if the self-renewing property of mouse KRMs is conserved in rats.
  • To validate cross-species KRM markers in a rat model.

Main Methods:

  • Parabiosis surgery was performed on inbred Lewis rats.
  • Cross-species KRM cell surface markers (CD81, C1q) were utilized.
  • Flow cytometry was used to analyze chimerism in various cell populations and KRMs.

Main Results:

  • Parabiosis induced significant chimerism in blood, spleen, and infiltrating kidney macrophages.
  • Rat KRMs exhibited minimal chimerism, indicating low dependence on peripheral blood.
  • CD81 and C1q markers effectively identified rat KRMs.

Conclusions:

  • Rat KRMs are maintained with little input from the peripheral blood.
  • The self-renewing nature of KRMs is conserved between mice and rats.
  • This study validates a key characteristic of KRMs across species.