title: Notch-Hes1 pathway is required for the development of IL-17-producing γδ T cells.
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.
authors: Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan. k_shibata@bioreg.kyushu-u.ac.jp
authors: Kensuke
authors: K
authors: Shibata
authors: Hisakata
authors: H
authors: Yamada
authors: Tetsuya
authors: T
authors: Sato
authors: Takashi
authors: T
authors: Dejima
authors: Masataka
authors: M
authors: Nakamura
authors: Tomokatsu
authors: T
authors: Ikawa
authors: Hiromitsu
authors: H
authors: Hara
authors: Sho
authors: S
authors: Yamasaki
authors: Ryoichiro
authors: R
authors: Kageyama
authors: Yoichiro
authors: Y
authors: Iwakura
authors: Hiroshi
authors: H
authors: Kawamoto
authors: Hiroyuki
authors: H
authors: Toh
authors: Yasunobu
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authors: Yoshikai