T-bet and RORα control lymph node formation by regulating embryonic innate lymphoid cell differentiation.

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:

09 Nov 2021 08:21

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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