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

Tracy S.H. In; Ashton Trotman-Grant; Shawn P. Fahl; Edward L.Y. Chen; Payam Zarin; Amanda J. Moore; David 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

Tracy S.H. In
, Ashton Trotman-Grant
, Shawn P. Fahl
, Edward L.Y. Chen
, Payam Zarin
, Amanda J. Moore
, David Wiest
, Juan Carlos Zúñiga-Pflücker
, Michele K. Anderson

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

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.

Original language	English
Article number	2004
Pages (from-to)	2004
Journal	Nature Communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-02225-5
State	Published - Dec 1 2017

Keywords

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
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
SOXC Transcription Factors/metabolism

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10.1038/s41467-017-02225-5

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title = "HEB is required for the specification of fetal IL-17-producing γδ T cells",

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.",

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author = "In, \{Tracy S.H.\} and Ashton Trotman-Grant and Fahl, \{Shawn P.\} and Chen, \{Edward L.Y.\} and Payam Zarin and Moore, \{Amanda J.\} and David Wiest and Z{\'u}{\~n}iga-Pfl{\"u}cker, \{Juan Carlos\} and Anderson, \{Michele K.\}",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

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doi = "10.1038/s41467-017-02225-5",

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AU - In, Tracy S.H.

AU - Trotman-Grant, Ashton

AU - Fahl, Shawn P.

AU - Chen, Edward L.Y.

AU - Zarin, Payam

AU - Moore, Amanda J.

AU - Wiest, David

AU - Zúñiga-Pflücker, Juan Carlos

AU - Anderson, Michele K.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

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KW - Animals

KW - Autoantigens/metabolism

KW - Basic Helix-Loop-Helix Transcription Factors/physiology

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KW - Female

KW - Fetal Development/immunology

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KW - Intraepithelial Lymphocytes/physiology

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KW - Mice

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KW - Mice, Knockout

KW - Models, Animal

KW - Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism

KW - Receptors, Antigen, T-Cell, gamma-delta/genetics

KW - SOXC Transcription Factors/metabolism

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U2 - 10.1038/s41467-017-02225-5

DO - 10.1038/s41467-017-02225-5

M3 - Article

C2 - 29222418

SN - 2041-1723

VL - 8

SP - 2004

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2004

ER -

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

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Keywords

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