A network of high-mobility group box transcription factors programs innate interleukin-17 production
Department of Pathology; Department of Medicine
SOXC Transcription Factors; Interleukin-17; Immunity, Innate
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.
DOI of Published Version
Immunity. 2013 Apr 18;38(4):681-93. doi: 10.1016/j.immuni.2013.01.010. Link to article on publisher's site
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.; and Kang, Joonsoo, "A network of high-mobility group box transcription factors programs innate interleukin-17 production" (2013). University of Massachusetts Medical School Faculty Publications. 86.