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

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    Authors
    Malhotra, Nidhi
    Narayan, 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
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    UMass Chan Affiliations
    Department of Medicine
    Department of Pathology
    Document Type
    Journal Article
    Publication Date
    2013-04-18
    Keywords
    SOXC Transcription Factors
    Interleukin-17
    Immunity, Innate
    Immunity
    
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    Link to Full Text
    http://dx.doi.org/10.1016/j.immuni.2013.01.010
    Abstract
    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 site
    DOI
    10.1016/j.immuni.2013.01.010
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/30582
    PubMed ID
    23562159
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.immuni.2013.01.010
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