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

Joshua D'Rozario; Konstantin Knoblich; Mechthild Lütge; Christian Pérez Shibayama; Hung-Wei Cheng; Yannick O Alexandre; David Roberts; Joana Campos; Emma E Dutton; Muath Suliman; Alice E Denton; Shannon J Turley; Richard L Boyd; Scott N Mueller; Burkhard Ludewig; Tracy S P Heng; Anne L Fletcher

doi:10.1002/eji.202250355

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

Eur J Immunol. 2023 Sep;53(9):e2250355. doi: 10.1002/eji.202250355. Epub 2023 Jul 12.

Authors

Joshua D'Rozario^{1

2

3}, Konstantin Knoblich^{1

3}, Mechthild Lütge⁴, Christian Pérez Shibayama⁴, Hung-Wei Cheng⁴, Yannick O Alexandre⁵, David Roberts³, Joana Campos⁶, Emma E Dutton³, Muath Suliman³, Alice E Denton⁷, Shannon J Turley⁸, Richard L Boyd⁹, Scott N Mueller⁵, Burkhard Ludewig⁴, Tracy S P Heng^#^{2

10}, Anne L Fletcher^#^{1

3}

Affiliations

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.

^# Contributed equally.

Abstract

The 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.

Keywords: CSF1; Fibroblastic reticular cells; Human lymph nodes; Lymph node stromal cells; Macrophages.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Fibroblasts*
Humans
Lymph Nodes
Macrophages
Mice
Signal Transduction*

Abstract

Publication types

MeSH terms

Grants and funding