A network of high-mobility group box transcription factors programs innate interleukin-17 production.
Immunity
; 38(4): 681-93, 2013 Apr 18.
Article
em En
| MEDLINE
| ID: mdl-23562159
ABSTRACT
How innate lymphoid cells (ILCs) in the thymus and gut become specialized effectors is unclear. The prototypic innate-like γδ T cells (Tγδ17) are a major source of interleukin-17 (IL-17). We demonstrate that Tγδ17 cells are programmed by a gene regulatory network consisting of a quartet of high-mobility group (HMG) box transcription factors, SOX4, SOX13, TCF1, and LEF1, and not by conventional TCR signaling. SOX4 and SOX13 directly regulated the two requisite Tγδ17 cell-specific genes, Rorc and Blk, whereas TCF1 and LEF1 countered the SOX proteins and induced genes of alternate effector subsets. The T cell lineage specification factor TCF1 was also indispensable for the generation of IL-22 producing gut NKp46(+) ILCs and restrained cytokine production by lymphoid tissue inducer-like effectors. These results indicate that similar gene network architecture programs innate sources of IL-17, independent of anatomical origins.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Grupo de Alta Mobilidade
/
Linfócitos T
/
Subpopulações de Linfócitos
/
Interleucina-17
/
Intestinos
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article