Abstract
Unlike conventional T cells, which are exported from the thymus as naive cells and acquire effector functions upon antigen encounter in the periphery, a subset of γδ T cells differentiates into effectors that produce IL-17 within the fetal thymus. We demonstrate here that intrathymic development of the naturally occurring IL-17-producing γδ T cells is independent of STAT3 and partly dependent on RORγt. Comparative gene-expression analysis identified Hes1, one of the basic helix-loop-helix proteins involved in Notch signaling, as a factor specifically expressed in IL-17-producing γδ T cells. Hes1 is critically involved in the development of IL-17-producing γδ T cells, as evidenced by their severe decrease in the thymi of Hes1-deficient fetal mice. Delta-like 4 (Dll4)-expressing stromal cells support the development of IL-17-producing γδ T cells in vitro. In addition, conditional Hes1 ablation in peripheral γδ T cells decreases their IL-17 production but not their IFN-γ production. These results reveal a unique differentiation pathway of IL-17-producing γδ T cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism*
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Cell Differentiation / immunology
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Female
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Interleukin-17 / metabolism*
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Male
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Mice
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Mice, Transgenic
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Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
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Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
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Receptors, Antigen, T-Cell, gamma-delta / metabolism
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Receptors, Notch / metabolism
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / metabolism
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Signal Transduction / immunology*
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Th17 Cells / cytology
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Th17 Cells / physiology*
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Thymus Gland / cytology*
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Thymus Gland / physiology
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Transcription Factor HES-1
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Hes1 protein, mouse
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Homeodomain Proteins
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Interleukin-17
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Antigen, T-Cell, gamma-delta
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Receptors, Notch
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STAT3 Transcription Factor
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Stat3 protein, mouse
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Transcription Factor HES-1