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Cx3cr1 controls kidney resident macrophage heterogeneity

Authors :
Alex Yashchenko
Sarah J. Bland
Cheng J. Song
Ummey Khalecha Bintha Ahmed
Rachel Sharp
Isabella G. Darby
Audrey M. Cordova
Morgan E. Smith
Jeremie M. Lever
Zhang Li
Ernald J. Aloria
Shuja Khan
Bibi Maryam
Shanrun Liu
Michael R. Crowley
Kenneth L. Jones
Lauren A. Zenewicz
James F. George
Michal Mrug
David K. Crossman
Katharina Hopp
Stavros Stavrakis
Mary B. Humphrey
Florent Ginhoux
Kurt A. Zimmerman
Source :
Frontiers in Immunology, Vol 14 (2023)
Publication Year :
2023
Publisher :
Frontiers Media S.A., 2023.

Abstract

Kidney macrophages are comprised of both monocyte-derived and tissue resident populations; however, the heterogeneity of kidney macrophages and factors that regulate their heterogeneity are poorly understood. Herein, we performed single cell RNA sequencing (scRNAseq), fate mapping, and parabiosis to define the cellular heterogeneity of kidney macrophages in healthy mice. Our data indicate that healthy mouse kidneys contain four major subsets of monocytes and two major subsets of kidney resident macrophages (KRM) including a population with enriched Ccr2 expression, suggesting monocyte origin. Surprisingly, fate mapping data using the newly developed Ms4a3Cre Rosa Stopf/f TdT model indicate that less than 50% of Ccr2+ KRM are derived from Ly6chi monocytes. Instead, we find that Ccr2 expression in KRM reflects their spatial distribution as this cell population is almost exclusively found in the kidney cortex. We also identified Cx3cr1 as a gene that governs cortex specific accumulation of Ccr2+ KRM and show that loss of Ccr2+ KRM reduces the severity of cystic kidney disease in a mouse model where cysts are mainly localized to the kidney cortex. Collectively, our data indicate that Cx3cr1 regulates KRM heterogeneity and niche-specific disease progression.

Details

Language :
English
ISSN :
16643224
Volume :
14
Database :
Directory of Open Access Journals
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
edsdoj.33bd5d09e8bc4889bac131cdfd30c35a
Document Type :
article
Full Text :
https://doi.org/10.3389/fimmu.2023.1082078