Stehle, Christina; Rückert, Timo; Fiancette, Rémi; Gajdasik, Dominika W; Willis, Claire; Ulbricht, Carolin; Durek, Pawel; Mashreghi, Mir-Farzin; Finke, Daniela; Hauser, Anja Erika; Withers, David R; Chang, Hyun-Dong; Zimmermann, Jakob; Romagnani, Chiara (2021). T-bet and RORα control lymph node formation by regulating embryonic innate lymphoid cell differentiation. Nature immunology, 22(10), pp. 1231-1244. Nature Publishing Group 10.1038/s41590-021-01029-6
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The generation of lymphoid tissues during embryogenesis relies on group 3 innate lymphoid cells (ILC3) displaying lymphoid tissue inducer (LTi) activity and expressing the master transcription factor RORγt. Accordingly, RORγt-deficient mice lack ILC3 and lymphoid structures, including lymph nodes (LN). Whereas T-bet affects differentiation and functions of ILC3 postnatally, the role of T-bet in regulating fetal ILC3 and LN formation remains completely unknown. Using multiple mouse models and single-cell analyses of fetal ILCs and ILC progenitors (ILCP), here we identify a key role for T-bet during embryogenesis and show that its deficiency rescues LN formation in RORγt-deficient mice. Mechanistically, T-bet deletion skews the differentiation fate of fetal ILCs and promotes the accumulation of PLZFhi ILCP expressing central LTi molecules in a RORα-dependent fashion. Our data unveil an unexpected role for T-bet and RORα during embryonic ILC function and highlight that RORγt is crucial in counteracting the suppressive effects of T-bet.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie |
UniBE Contributor: |
Zimmermann, Jakob |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1529-2908 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Rahel Fuhrer |
Date Deposited: |
09 Nov 2021 08:21 |
Last Modified: |
05 Dec 2022 15:54 |
Publisher DOI: |
10.1038/s41590-021-01029-6 |
PubMed ID: |
34556887 |
BORIS DOI: |
10.48350/160619 |
URI: |
https://boris.unibe.ch/id/eprint/160619 |
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