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

Nidhi Malhotra, Kavitha Narayan, Ok Hyun Cho, Katelyn Sylvia, Catherine C Yin, Heather J Melichar, Mehdi Rashighi, Veronique Lefebvre, John E Harris, Leslie J Berg, Joonsoo Kang, Emmanuel L Gautier, Claudia V Jakubzick, Gwendalyn J Randolph, J Adam Best, Jamie Knell, Ananda W Goldrath, Jennifer C Miller, Brian D Brown, Miriam MeradVladimir Jojic, Daphne Koller, Nadia R Cohen, Patrick J Brennan, Michael B Brenner, Tal Shay, Aviv Regev, Anne Fletcher, Kutlu G Elpek, Angelique Bellemare-Pelletier, Deepali Malhotra, Shannon J Turley, Radu Jianu, David H Laidlaw, Jim J Collins, Roi Gazit, Brian S Garrison, Derrick J Rossi, Francis S Kim, Tata N Rao, Amy Wagers, Susan A Shinton, Richard R Hardy, Paul Monach, Natalie A Bezman, Joseph C Sun, Charlie C Kim, Lewis L Lanier, Tracy S P Heng, Taras Kreslavsky, Michio W Painter, Jeffrey A Ericson, Scott P Davis, Diane Mathis, Christophe Benoist

Research output: Contribution to journalArticleResearchpeer-review

95 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)681 - 693
Number of pages13
Issue number4
Publication statusPublished - 2013
Externally publishedYes

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