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-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.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Tanaka Y,Hamano S,Gotoh K,Murata Y,Kunisaki Y,Nishikimi A,Takii R,Kawaguchi M,Inayoshi A,Masuko S,Himeno K,Sasazuki T,Fukui Ydoi
10.1038/ni1506subject
Has Abstractpub_date
2007-10-01 00:00:00pages
1067-75issue
10eissn
1529-2908issn
1529-2916pii
ni1506journal_volume
8pub_type
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