Store-Operated Ca2+ Entry Controls Clonal Expansion of T Cells through Metabolic Reprogramming.
Immunity
; 47(4): 664-679.e6, 2017 10 17.
Article
in En
| MEDLINE
| ID: mdl-29030115
ABSTRACT
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.
Key words
GLUT1; GLUT3; NFAT; ORAI1; SOCE; STIM1; STIM2; calcineurin; calcium; cell cycle; glycolysis; metabolism; mitochondria
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
Calcium Channels
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Calcium
/
Calcium Signaling
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2017
Type:
Article
Affiliation country:
United States