Critical regulation of follicular helper T cell differentiation and function by Gα 13 signaling
| Autor: | Jae-Ouk Kim, Young-hye Moon, Yeonseok Chung, Miso Park, Sang Geon Kim, Heeju Ryu, Keon Wook Kang, Da-Sol Kuen, Garam Choi |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Proceedings of the National Academy of Sciences. 118 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | GPCR-Gα protein-mediated signal transduction contributes to spatiotemporal interactions between immune cells to fine-tune and facilitate the process of inflammation and host protection. Beyond this, however, how Gα proteins contribute to the helper T cell subset differentiation and adaptive response have been underappreciated. Here, we found that Gα13 signaling in T cells plays a crucial role in inducing follicular helper T (Tfh) cell differentiation in vivo. T cell-specific Gα13-deficient mice have diminished Tfh cell responses in a cell-intrinsic manner in response to immunization, lymphocytic choriomeningitis virus infection, and allergen challenges. Moreover, Gα13-deficient Tfh cells express reduced levels of Bcl-6 and CXCR5 and are functionally impaired in their ability to adhere to and stimulate B cells. Mechanistically, Gα13-deficient Tfh cells harbor defective Rho-ROCK2 activation, and Rho agonist treatment recuperates Tfh cell differentiation and expression of Bcl-6 and CXCR5 in Tfh cells of T cell-specific Gα13-deficient mice. Conversely, ROCK inhibitor treatment hampers Tfh cell differentiation in wild-type mice. These findings unveil a crucial regulatory role of Gα13-Rho-ROCK axis in optimal Tfh cell differentiation and function, which might be a promising target for pharmacologic intervention in vaccine development as well as antibody-mediated immune disorders. |
| Databáze: | OpenAIRE |
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