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HEB is required for the specification of fetal IL-17-producing γδ T cells

Author

Listed:
  • Tracy S. H. In

    (Sunnybrook Research Institute
    Department of Immunology, University of Toronto)

  • Ashton Trotman-Grant

    (Sunnybrook Research Institute
    Department of Immunology, University of Toronto)

  • Shawn Fahl

    (Fox Chase Cancer Center)

  • Edward L. Y. Chen

    (Sunnybrook Research Institute
    Department of Immunology, University of Toronto)

  • Payam Zarin

    (Sunnybrook Research Institute
    Department of Immunology, University of Toronto)

  • Amanda J. Moore

    (Sunnybrook Research Institute
    Department of Immunology, University of Toronto)

  • David L. Wiest

    (Fox Chase Cancer Center)

  • Juan Carlos Zúñiga-Pflücker

    (Sunnybrook Research Institute
    Department of Immunology, University of Toronto)

  • Michele K. Anderson

    (Sunnybrook Research Institute
    Department of Immunology, University of Toronto)

Abstract

IL-17-producing γδ T (γδT17) 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− γδT17 cells. HEB is required in immature CD24+CD73− γδ 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+ γδ T cells, which are defective in RORγt expression and IL-17 production. Additionally, the fetal TCRγ chain repertoire is altered, and peripheral Vγ4 γδ T cells are mostly restricted to the IFNγ-producing phenotype in HEB-deficient mice. Therefore, our work identifies HEB-dependent pathways for the development of CD73+ and CD73− γδT17 cells, and provides mechanistic evidence for control of the γδT17 gene network by HEB.

Suggested Citation

  • Tracy S. H. In & Ashton Trotman-Grant & Shawn Fahl & Edward L. Y. Chen & Payam Zarin & Amanda J. Moore & David L. Wiest & Juan Carlos Zúñiga-Pflücker & Michele K. Anderson, 2017. "HEB is required for the specification of fetal IL-17-producing γδ T cells," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02225-5
    DOI: 10.1038/s41467-017-02225-5
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