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Cx3cr1 controls kidney resident macrophage heterogeneity
Alex Yashchenko1, Sarah J Bland1, Cheng J Song2
1Department of Internal Medicine, Division of Nephrology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
Frontiers in Immunology
|May 31, 2023
Summary
Healthy mouse kidneys have diverse macrophage populations. Cx3cr1 regulates kidney resident macrophage (KRM) heterogeneity and kidney disease progression, challenging previous assumptions about monocyte origins.
Area of Science:
- Immunology
- Renal Biology
- Cellular Heterogeneity
Background:
- Kidney macrophages comprise both monocyte-derived and tissue-resident populations.
- The heterogeneity of kidney macrophages and the factors regulating it remain poorly understood.
Purpose of the Study:
- To define the cellular heterogeneity of kidney macrophages in healthy mice.
- To investigate the factors regulating kidney resident macrophage (KRM) heterogeneity.
Main Methods:
- Single cell RNA sequencing (scRNAseq)
- Fate mapping (including novel Ms4a3 model)
- Parabiosis
Main Results:
- Identified four monocyte subsets and two KRM subsets in healthy mouse kidneys.
- Less than 50% of Ccr2+ KRM are derived from Ly6c^hi monocytes, contrary to expectations.
- Ccr2 expression in KRM correlates with kidney cortex localization, regulated by Cx3cr1.
- Loss of Ccr2+ KRM reduces severity in a kidney cortex-localized cystic kidney disease model.
Conclusions:
- Cx3cr1 plays a key role in regulating KRM heterogeneity and spatial distribution within the kidney.
- Cx3cr1 influences niche-specific disease progression, particularly in cortex-localized kidney diseases.
- This study redefines understanding of KRM origins and heterogeneity.
