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In TSH , Trotman-Grant A , Fahl S , Chen ELY , Zarin P , Moore AJ , Wiest DL , Zuniga-Pflucker JC , Anderson MK
HEB is required for the specification of fetal IL-17-producing gammadelta T cells
Nat Commun. 2017 Dec 8;8(1) :2004
PMID: 29222418    PMCID: PMC5722817   
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Abstract
IL-17-producing gammadelta T (gammadeltaT17) cells are critical components of the innate immune system. However, the gene networks that control their development are unclear. Here we show that HEB (HeLa E-box binding protein, encoded by Tcf12) is required for the generation of a newly defined subset of fetal-derived CD73(-) gammadeltaT17 cells. HEB is required in immature CD24(+)CD73(-) gammadelta T cells for the expression of Sox4, Sox13, and Rorc, and these genes are repressed by acute expression of the HEB antagonist Id3. HEB-deficiency also affects mature CD73(+) gammadelta T cells, which are defective in RORgammat expression and IL-17 production. Additionally, the fetal TCRgamma chain repertoire is altered, and peripheral Vgamma4 gammadelta T cells are mostly restricted to the IFNgamma-producing phenotype in HEB-deficient mice. Therefore, our work identifies HEB-dependent pathways for the development of CD73(+) and CD73(-) gammadeltaT17 cells, and provides mechanistic evidence for control of the gammadeltaT17 gene network by HEB.
Notes
2041-1723 In, Tracy S H Trotman-Grant, Ashton Fahl, Shawn Chen, Edward L Y Zarin, Payam Moore, Amanda J Wiest, David L Zuniga-Pflucker, Juan Carlos Anderson, Michele K ORCID: http://orcid.org/0000-0002-8820-5910 P01 AI102853/AI/NIAID NIH HHS/United States Journal Article England Nat Commun. 2017 Dec 8;8(1):2004. doi: 10.1038/s41467-017-02225-5.