RORα is a critical checkpoint for T cell and ILC2 commitment in the embryonic thymus.
Nat Immunol
; 22(2): 166-178, 2021 02.
Article
en En
| MEDLINE
| ID: mdl-33432227
ABSTRACT
Type 2 innate lymphoid cells (ILC2) contribute to immune homeostasis, protective immunity and tissue repair. Here we demonstrate that functional ILC2 cells can arise in the embryonic thymus from shared T cell precursors, preceding the emergence of CD4+CD8+ (double-positive) T cells. Thymic ILC2 cells migrated to mucosal tissues, with colonization of the intestinal lamina propria. Expression of the transcription factor RORα repressed T cell development while promoting ILC2 development in the thymus. From RNA-seq, assay for transposase-accessible chromatin sequencing (ATAC-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq) data, we propose a revised transcriptional circuit to explain the co-development of T cells and ILC2 cells from common progenitors in the thymus. When Notch signaling is present, BCL11B dampens Nfil3 and Id2 expression, permitting E protein-directed T cell commitment. However, concomitant expression of RORα overrides the repression of Nfil3 and Id2 repression, allowing ID2 to repress E proteins and promote ILC2 differentiation. Thus, we demonstrate that RORα expression represents a critical checkpoint at the bifurcation of the T cell and ILC2 lineages in the embryonic thymus.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Timo
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Linfocitos T CD4-Positivos
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Diferenciación Celular
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Linfocitos T CD8-positivos
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Linaje de la Célula
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Miembro 1 del Grupo F de la Subfamilia 1 de Receptores Nucleares
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Timocitos
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Inmunidad Innata
Límite:
Animals
Idioma:
En
Año:
2021
Tipo del documento:
Article