A network of high-mobility group box transcription factors programs innate interleukin-17 production
Cho, Ok Hyun
Sylvia, Katelyn E.
Yin, Catherine C.
Melichar, Heather J.
Harris, John E.
Berg, Leslie J.
Document TypeJournal Article
MetadataShow full item record
AbstractHow innate lymphoid cells (ILCs) in the thymus and gut become specialized effectors is unclear. The prototypic innate-like gammadelta T cells (Tgammadelta17) are a major source of interleukin-17 (IL-17). We demonstrate that Tgammadelta17 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 Tgammadelta17 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.
SourceImmunity. 2013 Apr 18;38(4):681-93. doi: 10.1016/j.immuni.2013.01.010. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/30582
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