Nature Immunology 8, 1067 - 1075 (2007)
Published online: 2 September 2007 | doi:10.1038/ni1506
T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor- subunit controlled by the Rac activator Dock2
Yoshihiko Tanaka1, Shinjiro Hamano2, Kazuhito Gotoh1, Yuzo Murata3, Yuya Kunisaki1, Akihiko Nishikimi1, Ryosuke Takii1, Makiko Kawaguchi1, Ayumi Inayoshi1, Sadahiko Masuko3, Kunisuke Himeno2, Takehiko Sasazuki4 & Yoshinori Fukui1
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-4R 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-4R. Thus, Dock2 links T cell receptor signals to downregulation of IL-4R to control the lineage commitment of CD4+ T cells.
- Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation and Department of Parasitology, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
- Department of Parasitology, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
- Department of Anatomy and Physiology, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
- International Medical Center of Japan, Tokyo 162-8655, Japan.
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