Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May;22(5):571-585.
doi: 10.1038/s41590-021-00920-6. Epub 2021 Apr 26.

Gremlin 1+ fibroblastic niche maintains dendritic cell homeostasis in lymphoid tissues

Varun N Kapoor #  1 , Sören Müller #  2 , Shilpa Keerthivasan  1 , Markus Brown  1 , Cecile Chalouni  3 , Elaine E Storm  4 , Alessandra Castiglioni  1 , Ryan Lane  1 , Maximilian Nitschke  5 , Claudia X Dominguez  1 , Jillian L Astarita  1 , Akshay T Krishnamurty  1 , Catherine B Carbone  1 , Yasin Senbabaoglu  2 , Amber W Wang  2 , Xiumin Wu  6 , Viviana Cremasco  7   8 , Merone Roose-Girma  5 , Lucinda Tam  5 , Jonas Doerr  6 , Mark Z Chen  9 , Wyne P Lee  9 , Zora Modrusan  10 , Yeqing Angela Yang  10 , Richard Bourgon  2 , Wendy Sandoval  10 , Andrey S Shaw  5 , Frederic J de Sauvage  4 , Ira Mellman  1 , Christine Moussion  1 , Shannon J Turley  11
Affiliations

Gremlin 1+ fibroblastic niche maintains dendritic cell homeostasis in lymphoid tissues

Varun N Kapoor et al. Nat Immunol. 2021 May.

Abstract

Fibroblastic reticular cells (FRCs) are specialized stromal cells that define tissue architecture and regulate lymphocyte compartmentalization, homeostasis, and innate and adaptive immunity in secondary lymphoid organs (SLOs). In the present study, we used single-cell RNA sequencing (scRNA-seq) of human and mouse lymph nodes (LNs) to identify a subset of T cell-zone FRCs defined by the expression of Gremlin1 (Grem1) in both species. Grem1-CreERT2 knock-in mice enabled localization, multi-omics characterization and genetic depletion of Grem1+ FRCs. Grem1+ FRCs primarily localize at T-B cell junctions of SLOs, neighboring pre-dendritic cells and conventional dendritic cells (cDCs). As such, their depletion resulted in preferential loss and decreased homeostatic proliferation and survival of resident cDCs and compromised T cell immunity. Trajectory analysis of human LN scRNA-seq data revealed expression similarities to murine FRCs, with GREM1+ cells marking the endpoint of both trajectories. These findings illuminate a new Grem1+ fibroblastic niche in LNs that functions to maintain the homeostasis of lymphoid tissue-resident cDCs.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Fletcher, A. L., Acton, S. E. & Knoblich, K. Lymph node fibroblastic reticular cells in health and disease. Nat. Rev. Immunol. 15, 350–361 (2015). - PubMed - PMC - DOI
    1. Malhotra, D., Fletcher, A. L. & Turley, S. J. Stromal and hematopoietic cells in secondary lymphoid organs: partners in immunity. Immunol. Rev. 251, 160–176 (2013). - PubMed - PMC - DOI
    1. Rodda, L. B., Bannard, O., Ludewig, B., Nagasawa, T. & Cyster, J. G. Phenotypic and morphological properties of germinal center dark zone Cxcl12-expressing reticular cells. J. Immunol. 195, 4781–4791 (2015). - PubMed - DOI
    1. Cremasco, V. et al. B cell homeostasis and follicle confines are governed by fibroblastic reticular cells. Nat. Immunol. 15, 973–981 (2014). - PubMed - PMC - DOI
    1. Link, A. et al. Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells. Nat. Immunol. 8, 1255–1265 (2007). - PubMed - DOI

Publication types

MeSH terms

Substances

LinkOut - more resources