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Intestinal fibroblastic reticular cell niches control innate lymphoid cell homeostasis and function

Hung-Wei Cheng, Mörbe Urs, Mechthild Lütge, Céline Engetschwiler, Lucas Onder, M Novkovic , Cristina Gil Cruz, Christian Perez Shibayama, T Hehlgans, Elke Scandella & Burkhard Ludewig

abstract Innate lymphoid cells (ILCs) govern immune cell homeostasis in the intestine and protect the host against microbial pathogens. Various cell-intrinsic pathways have been identified that determine ILC development and differentiation. However, the cellular components that regulate ILC sustenance and function in the intestinal lamina propria are less known. Using single-cell transcriptomic analysis of lamina propria fibroblasts, we identify fibroblastic reticular cells (FRCs) that underpin cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Genetic ablation of lymphotoxin-β receptor expression in Ccl19-expressing FRCs blocks the maturation of CPs into mature ILFs. Interactome analysis shows the major niche factors and processes underlying FRC-ILC crosstalk. In vivo validation confirms that a sustained lymphotoxin-driven feedforward loop of FRC activation including IL-7 generation is critical for the maintenance of functional ILC populations. In sum, our study indicates critical fibroblastic niches within the intestinal lamina propria that control ILC homeostasis and functionality and thereby secure protective gut immunity.
citation Cheng H W, Urs M , Lütge M, Engetschwiler C, Onder L, Novkovic M, Gil Cruz C, Perez Shibayama C, Hehlgans T, Scandella E, Ludewig B. Intestinal fibroblastic reticular cell niches control innate lymphoid cell homeostasis and function. Nat Commun 2022; 13:2027.
type journal paper/review (English)
date of publishing 19-4-2022
journal title Nat Commun (13/1)
ISSN electronic 2041-1723
pages 2027
PubMed 35440118
DOI 10.1038/s41467-022-29734-2
contact Christian Perez Shibayama