The hippo kinase MST1 negatively regulates the differentiation of follicular helper T cells. Issue 3 (26th October 2022)

• Record Type: Journal Article
• Authors: Dong, Lin; Cao, Yejin; Yang, Hui; Hou, Yueru; He, Ying; Wang, Yufei; Yang, Qiuli; Bi, Yujing; Liu, Guangwei
• Is Part Of: Immunology. Volume 168:Issue 3(2023)
• Page Start: 511
• Page End: 525
• Publication Date: 2022-10-26
• Subjects: follicular helper T cells -- GC reaction -- infectious diseases -- kinase MST1 -- metabolism -- T cell differentiation -- TFH -- virus infection; Immunology -- Periodicals
• DOI: 10.1111/imm.13590
• Languages: English
• ISSNs: 0019-2805

Abstract

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. Abstract : MST1 deficiency promotes TFH cell differentiation through mTOR‐HIF1α metabolic activities coupled with the Foxo3 signaling pathway.