The hippo kinase MST1 negatively regulates the differentiation of follicular helper T cells |
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| Authors: | Lin Dong Yejin Cao Hui Yang Yueru Hou Ying He Yufei Wang Qiuli Yang Yujing Bi Guangwei Liu |
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| Institution: | 1. Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China;2. Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China;3. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China |
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| Abstract: | Follicular helper T (TFH) cells are essential for inducing germinal centre (GC) reactions to mediate humoral adaptive immunity and antiviral effects, but the mechanisms of TFH cell differentiation remain unclear. Here, we found that the hippo kinase MST1 is critical for TFH cell differentiation, GC formation, and antibody production under steady-state conditions and viral infection. MST1 deficiency intrinsically enhanced TFH cell differentiation and GC reactions in vivo and in vitro. Mechanistically, mTOR and HIF1α signalling is involved in glucose metabolism and increased glycolysis and decreased OXPHOS, which are critically required for MST1 deficiency-directed TFH cell differentiation. Moreover, upregulated Foxo3 expression is critically responsible for TFH cell differentiation induced by Mst1−/−. Thus, our findings identify a previously unrecognized relationship between hippo kinase MST1 signalling and mTOR-HIF1α-metabolic reprogramming coupled with Foxo3 signalling in reprogramming TFH cell differentiation. |
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| Keywords: | follicular helper T cells GC reaction infectious diseases kinase MST1 metabolism T cell differentiation TFH virus infection |
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