Access

Article

Nature Immunology 8, 1067–1075 (1 October 2007) | doi:10.1038/ni1506

T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-|[alpha]| 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

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.