التفاصيل البيبلوغرافية
| العنوان: |
Critical regulation of follicular helper T cell differentiation and function by Gα13 signaling. |
| المؤلفون: |
Da-Sol Kuen, Miso Park, Heeju Ryu, Garam Choi, Young-Hye Moon, Jae-Ouk Kim, Keon Wook Kang, Sang Geon Kim, Yeonseok Chung |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 10/26/2021, Vol. 118 Issue 43, p1-10, 10p |
| مصطلحات موضوعية: |
T helper cells, T cell differentiation, CELL physiology, LYMPHOCYTIC choriomeningitis virus, CELL differentiation, CURCUMIN, COMMERCIAL products |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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