Cheng, Hung-Wei and Mörbe, Urs and Lütge, Mechthild and Engetschwiler, Celine and Onder, Lucas and Novkovic, Mario and Gil-Cruz, Cristina and Perez-Shibayama, Christian and Hehlgans, Thomas and Scandella, Elke and Ludewig, Burkhard (2022) Intestinal fibroblastic reticular cell niches control innate lymphoid cell homeostasis and function. NATURE COMMUNICATIONS, 13 (1): 2027. ISSN 2041-1723
Full text not available from this repository. (Request a copy)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-beta 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. Fibroblastic reticular cells (FRCs) support localisation of immune cells in secondary lymphoid tissues but less is known about the lamina propria. Here the authors use scRNA-seq and intestinal infection to characterise FRCs in the intestinal lamina propria and show specialised niches that foster innate lymphoid cells during homeostasis and infection.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ROR-GAMMA-T; STROMAL CELLS; NODE; EXPRESSION; GUT; TISSUES; DIFFERENTIATION; ORGANOGENESIS; MAINTENANCE; ACTIVATION |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Feb 2024 06:39 |
| Last Modified: | 15 Feb 2024 06:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/57557 |
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