University of Massachusetts Medical School Faculty Publications
Title
A network of high-mobility group box transcription factors programs innate interleukin-17 production
UMMS Affiliation
Department of Pathology; Department of Medicine
Publication Date
2013-04-18
Document Type
Article
Subjects
SOXC Transcription Factors; Interleukin-17; Immunity, Innate
Disciplines
Immunity
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.
DOI of Published Version
10.1016/j.immuni.2013.01.010
Source
Immunity. 2013 Apr 18;38(4):681-93. doi: 10.1016/j.immuni.2013.01.010. Link to article on publisher's site
Related Resources
Journal/Book/Conference Title
Immunity
PubMed ID
23562159
Repository Citation
Malhotra N, Narayan K, Cho OH, Sylvia KE, Yin CC, Melichar HJ, Rashighi M, Lefebvre V, Harris JE, Berg LJ, Kang J. (2013). A network of high-mobility group box transcription factors programs innate interleukin-17 production. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1016/j.immuni.2013.01.010. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/86