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Immunity. 2013 Apr 18;38(4):681-93. doi: 10.1016/j.immuni.2013.01.010. Epub 2013 Apr 4.

A network of high-mobility group box transcription factors programs innate interleukin-17 production.

Author information

1
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.

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.

PMID:
23562159
PMCID:
PMC3811080
DOI:
10.1016/j.immuni.2013.01.010
[Indexed for MEDLINE]
Free PMC Article

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