| First Author | Kim TD | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 2623 |
| PubMed ID | 28572627 | Mgi Jnum | J:274805 |
| Mgi Id | MGI:6296058 | Doi | 10.1038/s41598-017-02697-x |
| Citation | Kim TD, et al. (2017) MicroRNA-150 modulates intracellular Ca (2+) levels in naive CD8(+) T cells by targeting TMEM20. Sci Rep 7(1):2623 |
| abstractText | 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 naive CD8(+) T cells, are not fully defined. Here, we showed that microRNA-150 (miR-150) controls intracellular Ca(2+) levels in naive 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 naive 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 naive 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 naive CD8(+) T cells, which suggest a mechanism to overcome anergy induction by the regulation of intracellular Ca(2+) levels. |
