| First Author | Kong KF | Year | 2014 |
| Journal | Nat Immunol | Volume | 15 |
| Issue | 5 | Pages | 465-72 |
| PubMed ID | 24705298 | Mgi Jnum | J:209959 |
| Mgi Id | MGI:5569178 | Doi | 10.1038/ni.2866 |
| Citation | Kong KF, et al. (2014) Protein kinase C-eta controls CTLA-4-mediated regulatory T cell function. Nat Immunol 15(5):465-72 |
| abstractText | 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 PKC-eta associated with CTLA-4 and was recruited to the Treg cell IS. PKC-eta-deficient Treg cells displayed defective suppressive activity, including suppression of tumor immunity but not of autoimmune colitis. Phosphoproteomic and biochemical analysis revealed an association between CTLA-4-PKC-eta and the GIT2-alphaPIX-PAK complex, an IS-localized focal adhesion complex. Defective activation of this complex in PKC-eta-deficient Treg cells was associated with reduced depletion of CD86 from APCs by Treg cells. These results reveal a CTLA-4-PKC-eta signaling axis required for contact-dependent suppression and implicate this pathway as a potential cancer immunotherapy target. |
