T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-α subunit controlled by the Rac activator Dock2

Yoshihiko Tanaka, Shinjiro Hamano, Kazuhito Gotoh, Yuzo Murata, Yuya Kunisaki, Akihiko Nishikimi, Ryosuke Takii, Makiko Kawaguchi, Ayumi Inayoshi, Sadahiko Masuko, Kunisuke Himeno, Takehiko Sasazuki, Yoshinori Fukui

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48 Citations (Scopus)

Abstract

The lineage commitment of CD4+ T cells is coordinately regulated by signals through the T cell receptor and cytokine receptors, yet how these signals are integrated remains elusive. Here we find that mice lacking Dock2, a Rac activator in lymphocytes, developed allergic disease through a mechanism dependent on CD4+ T cells and the interleukin 4 receptor (IL-4R). Dock2-deficient CD4+ T cells showed impaired antigen-driven downregulation of IL-4Rα surface expression, resulting in sustained IL-4R signaling and excessive T helper type 2 responses. Dock2 was required for T cell receptor-mediated phosphorylation of the microtubule-destabilizing protein stathmin and for lysosomal trafficking and the degradation of IL-4Rα. Thus, Dock2 links T cell receptor signals to downregulation of IL-4Rα to control the lineage commitment of CD4+ T cells.

Original languageEnglish
Pages (from-to)1067-1075
Number of pages9
JournalNature Immunology
Volume8
Issue number10
DOIs
Publication statusPublished - Oct 1 2007

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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