Notch-Hes1 pathway is required for the development of IL-17-producing γδ T cells

Kensuke Shibata, Hisakata Yamada, Tetsuya Sato, Takashi Dejima, Masataka Nakamura, Tomokatsu Ikawa, Hiromitsu Hara, Sho Yamasaki, Ryoichiro Kageyama, Yoichiro Iwakura, Hiroshi Kawamoto, Hiroyuki Toh, Yasunobu Yoshikai

Research output: Contribution to journalArticlepeer-review

104 Citations (Scopus)

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 geneexpression 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.

Original languageEnglish
Pages (from-to)586-593
Number of pages8
JournalBlood
Volume118
Issue number3
DOIs
Publication statusPublished - 21-07-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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