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oai:uvadoc.uva.es:10324/643012024-12-16T09:04:16Zcom_10324_1134com_10324_931com_10324_894col_10324_1213

2024-01-08T14:33:26Z urn:hdl:10324/64301 Protein kinase C-η controls CTLA-4–mediated regulatory T cell function Kong, Kok-Fai Fu, Guo Zhang, Yaoyang Yokosuka, Tadashi Casas Requena, Javier Canonigo-Balancio, Ann J Becart, Stephane Kim, Gisen Yates, John R Kronenberg, Mitchell Saito, Takashi Gascoigne, Nicholas R J Altman, Amnon Producción Científica 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-η associated with CTLA-4 and was recruited to the Treg cell IS. PKC-η-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-η and the GIT2-αPIX-PAK complex, an IS-localized focal adhesion complex. Defective activation of this complex in PKC-η-deficient Treg cells was associated with reduced depletion of CD86 from APCs by Treg cells. These results reveal a CTLA-4-PKC-η signaling axis required for contact-dependent suppression and implicate this pathway as a potential cancer immunotherapy target. 2024-01-08T14:33:26Z 2024-01-08T14:33:26Z 2014 info:eu-repo/semantics/article Nature Immunology 15:465–472. https://doi.org/10.1038/ni.2866 1529-2908 https://uvadoc.uva.es/handle/10324/64301 10.1038/ni.2866 465 5 472 Nature Immunology 15 1529-2916 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/4.0/ Atribución 4.0 Internacional