MicroRNA-150 modulates intracellular Ca(2+) levels in naïve CD8(+) T cells by targeting TMEM20

Regulation of intracellular Ca(2+) signaling is a major determinant of CD8(+) T cell responsiveness, but the mechanisms underlying this regulation of Ca(2+) levels, especially in naïve CD8(+) T cells, are not fully defined. Here, we showed that microRNA-150 (miR-150) controls intracellular Ca(2+) levels in naïve CD8(+) T cells required for activation by suppressing TMEM20, a negative regulator of Ca(2+) extrusion. miR-150 deficiency increased TMEM20 expression, which resulted in increased intracellular Ca(2+) levels in naïve CD8(+) T cells. The subsequent increase in Ca(2+) levels induced expression of anergy-inducing genes, such as Cbl-b, Egr2, and p27, through activation of NFAT1, as well as reduced cell proliferation, cytokine production, and the antitumor activity of CD8(+) T cells upon antigenic stimulation. The anergy-promoting molecular milieu and function induced by miR-150 deficiency were rescued by reinstatement of miR-150. Additionally, knockdown of TMEM20 in miR-150-deficient naïve CD8(+) T cells reduced intracellular Ca(2+) levels. Our findings revealed that miR-150 play essential roles in controlling intracellular Ca(2+) level and activation in naïve CD8(+) T cells, which suggest a mechanism to overcome anergy induction by the regulation of intracellular Ca(2+) levels.