Protein kinase C-η controls CTLA-4-mediated regulatory T cell function.

Regulatory T (Treg) cells, which maintain immune homeostasis and self-tolerance, form an immunological synapse (IS) with antigen-presenting cells (APCs). However, signaling events at the Treg cell IS remain unknown. Here we show that the kinase associated with CTLA-4 and was recruited to the Treg cell IS. Treg cells displayed defective suppressive activity, including suppression of tumor immunity but not of autoimmune colitis. Phosphoproteomic and biochemical analysis revealed an association between and the GIT2-αPIX-PAK complex, an IS-localized focal adhesion complex. Defective activation of this complex in duanyu1531-η-deficient Treg cells was associated with reduced depletion of CD86 from APCs by Treg cells. These results reveal a CTLA-4-duanyu1531-η signaling axis required for contact-dependent suppression and implicate this pathway as a potential cancer immunotherapy target.

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