Fibroblastic reticular cells provide a supportive niche for lymph node–resident macrophages

Author:

D'Rozario Joshua123,Knoblich Konstantin13,Lütge Mechthild4,Shibayama Christian Pérez4,Cheng Hung‐Wei4,Alexandre Yannick O.5,Roberts David3,Campos Joana6,Dutton Emma E.3,Suliman Muath3,Denton Alice E.7,Turley Shannon J.8,Boyd Richard L.9,Mueller Scott N.5ORCID,Ludewig Burkhard4,Heng Tracy S.P.210,Fletcher Anne L.13ORCID

Affiliation:

1. Department of Biochemistry and Molecular Biology and Monash Biomedicine Discovery Institute Monash University Clayton Australia

2. Department of Anatomy and Developmental Biology Monash Biomedicine Discovery Institute Monash University Clayton Australia

3. Institute of Immunology and Immunotherapy University of Birmingham Birmingham UK

4. Institute of Immunobiology Kantonsspital St. Gallen St. Gallen Switzerland

5. Department of Microbiology and Immunology The Peter Doherty Institute for Infection and Immunity The University of Melbourne VIC Melbourne Australia

6. Institute of Inflammation and Ageing University of Birmingham Birmingham UK

7. Department of Immunology and Inflammation Imperial College London London UK

8. Department of Cancer Immunology Genentech Inc. South San Francisco CA USA

9. Cartherics Pty Ltd Hudson Institute for Medical Research Clayton Australia

10. ARC Training Centre for Cell and Tissue Engineering Technologies Monash University Clayton Australia

Abstract

AbstractThe lymph node (LN) is home to resident macrophage populations that are essential for immune function and homeostasis, but key factors controlling this niche are undefined. Here, we show that fibroblastic reticular cells (FRCs) are an essential component of the LN macrophage niche. Genetic ablation of FRCs caused rapid loss of macrophages and monocytes from LNs across two in vivo models. Macrophages co‐localized with FRCs in human LNs, and murine single‐cell RNA‐sequencing revealed that FRC subsets broadly expressed master macrophage regulator CSF1. Functional assays containing purified FRCs and monocytes showed that CSF1R signaling was sufficient to support macrophage development. These effects were conserved between mouse and human systems. These data indicate an important role for FRCs in maintaining the LN parenchymal macrophage niche.

Funder

Australian Research Council

Publisher

Wiley

Subject

Immunology,Immunology and Allergy

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