[PDF][PDF] Store-operated Ca2+ entry controls clonal expansion of T cells through metabolic reprogramming

M Vaeth, M Maus, S Klein-Hessling, E Freinkman… - Immunity, 2017 - cell.com
M Vaeth, M Maus, S Klein-Hessling, E Freinkman, J Yang, M Eckstein, S Cameron
Immunity, 2017cell.com
Summary Store-operated Ca 2+ entry (SOCE) is the main Ca 2+ influx pathway in
lymphocytes and is essential for T cell function and adaptive immunity. SOCE is mediated by
Ca 2+ release-activated Ca 2+(CRAC) channels that are activated by stromal interaction
molecule (STIM) 1 and STIM2. SOCE regulates many Ca 2+-dependent signaling
molecules, including calcineurin, and inhibition of SOCE or calcineurin impairs antigen-
dependent T cell proliferation. We here report that SOCE and calcineurin regulate cell cycle …
Summary
Store-operated Ca2+ entry (SOCE) is the main Ca2+ influx pathway in lymphocytes and is essential for T cell function and adaptive immunity. SOCE is mediated by Ca2+ release-activated Ca2+ (CRAC) channels that are activated by stromal interaction molecule (STIM) 1 and STIM2. SOCE regulates many Ca2+-dependent signaling molecules, including calcineurin, and inhibition of SOCE or calcineurin impairs antigen-dependent T cell proliferation. We here report that SOCE and calcineurin regulate cell cycle entry of quiescent T cells by controlling glycolysis and oxidative phosphorylation. SOCE directs the metabolic reprogramming of naive T cells by regulating the expression of glucose transporters, glycolytic enzymes, and metabolic regulators through the activation of nuclear factor of activated T cells (NFAT) and the PI3K-AKT kinase-mTOR nutrient-sensing pathway. We propose that SOCE controls a critical "metabolic checkpoint" at which T cells assess adequate nutrient supply to support clonal expansion and adaptive immune responses.
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