Journal
BLOOD
Volume 118, Issue 3, Pages 586-593Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-02-334995
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Funding
- Japan Society for Promotion of Science
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Founding Research Centers for Emerging and Reemerging Infectious Diseases
- Grants-in-Aid for Scientific Research [22118004, 21240028, 22021032, 22790468, 21390130] Funding Source: KAKEN
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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 gamma delta 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 gamma delta T cells is independent of STAT3 and partly dependent on ROR gamma t. 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 gamma delta T cells. Hes1 is critically involved in the development of IL-17-producing gamma delta 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 gamma delta T cells in vitro. In addition, conditional Hes1 ablation in peripheral gamma delta T cells decreases their IL-17 production but not their IFN-gamma production. These results reveal a unique differentiation pathway of IL-17-producing gamma delta T cells. (Blood. 2011;118(3):586-593)
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