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

Journal Paper/Review - Apr 19, 2022

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Citation
Cheng H, Scandella E, Hehlgans T, Perez Shibayama C, Gil Cruz C, Novkovic M, Onder L, Engetschwiler C, Lütge M, Mörbe U, Ludewig B. Intestinal fibroblastic reticular cell niches control innate lymphoid cell homeostasis and function. Nat Commun 2022; 13:2027.
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Journal Paper/Review (English)
Journal
Nat Commun 2022; 13
Publication Date
Apr 19, 2022
Issn Print
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2041-1723
Pages
2027
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Brief description/objective

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.