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 Gotou, Yuzo Murata, Yuya Kunisaki, Akihiko Nishikimi, Ryosuke Takii, Makiko Kawaguchi, Ayumi Inayoshi, Sadahiko Masuko, Kunisuke Himeno, Takehiko Sasazuki, Yoshinori Fukui

Research output: Contribution to journalArticle

47 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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Interleukin-4 Receptors
T-Cell Antigen Receptor
T-Lymphocytes
Down-Regulation
Stathmin
Microtubule Proteins
Cytokine Receptors
Phosphorylation
Lymphocytes
Antigens

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-α subunit controlled by the Rac activator Dock2. / Tanaka, Yoshihiko; Hamano, Shinjiro; Gotou, Kazuhito; Murata, Yuzo; Kunisaki, Yuya; Nishikimi, Akihiko; Takii, Ryosuke; Kawaguchi, Makiko; Inayoshi, Ayumi; Masuko, Sadahiko; Himeno, Kunisuke; Sasazuki, Takehiko; Fukui, Yoshinori.

In: Nature Immunology, Vol. 8, No. 10, 01.10.2007, p. 1067-1075.

Research output: Contribution to journalArticle

Tanaka, Y, Hamano, S, Gotou, K, Murata, Y, Kunisaki, Y, Nishikimi, A, Takii, R, Kawaguchi, M, Inayoshi, A, Masuko, S, Himeno, K, Sasazuki, T & Fukui, Y 2007, 'T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-α subunit controlled by the Rac activator Dock2', Nature Immunology, vol. 8, no. 10, pp. 1067-1075. https://doi.org/10.1038/ni1506
Tanaka, Yoshihiko ; Hamano, Shinjiro ; Gotou, Kazuhito ; Murata, Yuzo ; Kunisaki, Yuya ; Nishikimi, Akihiko ; Takii, Ryosuke ; Kawaguchi, Makiko ; Inayoshi, Ayumi ; Masuko, Sadahiko ; Himeno, Kunisuke ; Sasazuki, Takehiko ; Fukui, Yoshinori. / T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-α subunit controlled by the Rac activator Dock2. In: Nature Immunology. 2007 ; Vol. 8, No. 10. pp. 1067-1075.
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