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

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

doi:10.1038/s41467-017-02225-5

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

Nat Commun. 2017 Dec 8;8(1):2004. doi: 10.1038/s41467-017-02225-5.

Authors

Tracy S H In^{1

2}, Ashton Trotman-Grant^{1

2}, Shawn Fahl³, Edward L Y Chen^{1

2}, Payam Zarin^{1

2}, Amanda J Moore^{1

2}, David L Wiest³, Juan Carlos Zúñiga-Pflücker^{1

2}, Michele K Anderson^{4

5}

Affiliations

¹ Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
² Department of Immunology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
³ Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA.
⁴ Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada. [email protected].
⁵ Department of Immunology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. [email protected].

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

5'-Nucleotidase / metabolism
Animals
Autoantigens / metabolism
Basic Helix-Loop-Helix Transcription Factors / physiology*
Cell Differentiation
Female
Fetal Development / immunology*
Gene Expression Regulation, Developmental / immunology*
Immunity, Innate*
Interferon-gamma / metabolism
Interleukin-17 / immunology
Interleukin-17 / metabolism
Intraepithelial Lymphocytes / physiology*
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Models, Animal
Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
Receptors, Antigen, T-Cell, gamma-delta / genetics
Receptors, Antigen, T-Cell, gamma-delta / metabolism
SOXC Transcription Factors / metabolism

Substances

Autoantigens
Basic Helix-Loop-Helix Transcription Factors
Interleukin-17
Nuclear Receptor Subfamily 1, Group F, Member 3
Receptors, Antigen, T-Cell, gamma-delta
SOXC Transcription Factors
Sox13 protein, mouse
Sox4 protein, mouse
Tcf12 protein, mouse
Interferon-gamma
5'-Nucleotidase

Abstract

Publication types

MeSH terms

Substances

Grants and funding