A network of high-mobility group box transcription factors programs innate interleukin-17 production
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Authors
Malhotra, NidhiNarayan, Kavitha
Cho, Ok Hyun
Sylvia, Katelyn E.
Yin, Catherine C.
Melichar, Heather J.
Rashighi, Medhi
Lefebvre, Veronique
Harris, John E.
Berg, Leslie J.
Kang, Joonsoo
Document Type
Journal ArticlePublication Date
2013-04-18
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How 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.Source
Immunity. 2013 Apr 18;38(4):681-93. doi: 10.1016/j.immuni.2013.01.010. Link to article on publisher's siteDOI
10.1016/j.immuni.2013.01.010Permanent Link to this Item
http://hdl.handle.net/20.500.14038/30582PubMed ID
23562159Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.immuni.2013.01.010