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Protein Kinase C-η Controls CTLA-4-Mediated Regulatory T Cell Function
Regulatory T cells (T(reg) cells), which maintain immune homeostasis and self-tolerance, form an immunological synapse (IS) with antigen-presenting cells (APCs). However, signaling events at the T(reg) IS remain unknown. Here we show that protein kinase C-η (PKC-η) associated with CTLA-4 and was rec...
| Autores principales: | , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2014
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040250/ https://www.ncbi.nlm.nih.gov/pubmed/24705298 http://dx.doi.org/10.1038/ni.2866 |
| _version_ | 1782318560657276928 |
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| author | Kong, Kok-Fai Fu, Guo Zhang, Yaoyang Yokosuka, Tadashi Casas, Javier Canonigo-Balancio, Ann J. Becart, Stephane Kim, Gisen Yates, John R. Kronenberg, Mitchell Saito, Takashi Gascoigne, Nicholas R. J. Altman, Amnon |
| author_facet | Kong, Kok-Fai Fu, Guo Zhang, Yaoyang Yokosuka, Tadashi Casas, Javier Canonigo-Balancio, Ann J. Becart, Stephane Kim, Gisen Yates, John R. Kronenberg, Mitchell Saito, Takashi Gascoigne, Nicholas R. J. Altman, Amnon |
| author_sort | Kong, Kok-Fai |
| collection | PubMed |
| description | Regulatory T cells (T(reg) cells), which maintain immune homeostasis and self-tolerance, form an immunological synapse (IS) with antigen-presenting cells (APCs). However, signaling events at the T(reg) IS remain unknown. Here we show that protein kinase C-η (PKC-η) associated with CTLA-4 and was recruited to the T(reg) IS. PKC-η-deficient T(reg) cells displayed defective suppressive activity, including suppression of tumor immunity but not autoimmune colitis. Phosphoproteomic analysis revealed an association between CTLA-4-PKC-η and the GIT-PIX-PAK complex, an IS-localized focal adhesion complex. Defective activation of this complex in PKC-η-deficient T(reg) cells was associated with reduced CD86 depletion from APCs by T(reg) cells. These results reveal a novel CTLA-4-PKC-η signaling axis required for contact-dependent suppression, implicating this pathway as a potential cancer immunotherapy target. |
| format | Online Article Text |
| id | pubmed-4040250 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2014 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-40402502014-11-01 Protein Kinase C-η Controls CTLA-4-Mediated Regulatory T Cell Function Kong, Kok-Fai Fu, Guo Zhang, Yaoyang Yokosuka, Tadashi Casas, Javier Canonigo-Balancio, Ann J. Becart, Stephane Kim, Gisen Yates, John R. Kronenberg, Mitchell Saito, Takashi Gascoigne, Nicholas R. J. Altman, Amnon Nat Immunol Article Regulatory T cells (T(reg) cells), which maintain immune homeostasis and self-tolerance, form an immunological synapse (IS) with antigen-presenting cells (APCs). However, signaling events at the T(reg) IS remain unknown. Here we show that protein kinase C-η (PKC-η) associated with CTLA-4 and was recruited to the T(reg) IS. PKC-η-deficient T(reg) cells displayed defective suppressive activity, including suppression of tumor immunity but not autoimmune colitis. Phosphoproteomic analysis revealed an association between CTLA-4-PKC-η and the GIT-PIX-PAK complex, an IS-localized focal adhesion complex. Defective activation of this complex in PKC-η-deficient T(reg) cells was associated with reduced CD86 depletion from APCs by T(reg) cells. These results reveal a novel CTLA-4-PKC-η signaling axis required for contact-dependent suppression, implicating this pathway as a potential cancer immunotherapy target. 2014-04-06 2014-05 /pmc/articles/PMC4040250/ /pubmed/24705298 http://dx.doi.org/10.1038/ni.2866 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| spellingShingle | Article Kong, Kok-Fai Fu, Guo Zhang, Yaoyang Yokosuka, Tadashi Casas, Javier Canonigo-Balancio, Ann J. Becart, Stephane Kim, Gisen Yates, John R. Kronenberg, Mitchell Saito, Takashi Gascoigne, Nicholas R. J. Altman, Amnon Protein Kinase C-η Controls CTLA-4-Mediated Regulatory T Cell Function |
| title | Protein Kinase C-η Controls CTLA-4-Mediated Regulatory T Cell Function |
| title_full | Protein Kinase C-η Controls CTLA-4-Mediated Regulatory T Cell Function |
| title_fullStr | Protein Kinase C-η Controls CTLA-4-Mediated Regulatory T Cell Function |
| title_full_unstemmed | Protein Kinase C-η Controls CTLA-4-Mediated Regulatory T Cell Function |
| title_short | Protein Kinase C-η Controls CTLA-4-Mediated Regulatory T Cell Function |
| title_sort | protein kinase c-η controls ctla-4-mediated regulatory t cell function |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040250/ https://www.ncbi.nlm.nih.gov/pubmed/24705298 http://dx.doi.org/10.1038/ni.2866 |
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