T-bet and RORα control lymph node formation by regulating embryonic innate lymphoid cell differentiation.
Nat Immunol
; 22(10): 1231-1244, 2021 10.
Article
en En
| MEDLINE
| ID: mdl-34556887
ABSTRACT
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Linfocitos
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Diferenciación Celular
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Proteínas de Dominio T Box
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Miembro 1 del Grupo F de la Subfamilia 1 de Receptores Nucleares
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Inmunidad Innata
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Ganglios Linfáticos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Nat Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania