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mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation #MMPMID27637146
Zeng H; Cohen S; Guy C; Shrestha S; Neale G; Brown SA; Cloer C; Kishton RJ; Gao X; Youngblood B; Do M; Li MO; Locasale JW; Rathmell JC; Chi H
Immunity 2016[Sep]; 45 (3): 540-54 PMID27637146show ga
Follicular helper T (Tfh) cells are crucial for germinal center (GC)formation andhumoraladaptiveimmunity. Mechanisms underlying Tfh cell differentiation in peripheral and mucosal lymphoid organs are incompletely understood. We report here that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and GC reaction under steady state and after antigen immunization and viral infection. Loss of mTORC1 and mTORC2 in T cells exerted distinct effects on Tfh cell signature gene expression, whereas increased mTOR activity promoted Tfh responses. Deficiency of mTORC2 impaired CD4+ T cell accumulation and immunoglobulin A production and aberrantly induced the transcription factor Foxo1. Mechanistically, the costimulatory molecule ICOS activated mTORC1 and mTORC2 to drive glycolysis and lipogenesis, and glucose transporter 1-mediated glucose metabolism promoted Tfh cell responses. Altogether, mTOR acts as a central node in Tfh cells by linking immune signals to anabolic metabolism and transcriptional activity.