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Nat Immunol. 2007 Oct;8(10):1067-75. Epub 2007 Sep 2.

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

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Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, University, Fukuoka 812-8582, Japan.


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-4Ralpha 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-4Ralpha. Thus, Dock2 links T cell receptor signals to downregulation of IL-4Ralpha to control the lineage commitment of CD4+ T cells.

[Indexed for MEDLINE]

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