Open AccessMicroRNA-150 modulates intracellular Ca 2+ levels in naïve CD8+ T cells by targeting TMEM20
Author(s) -
TaeDon Kim,
Hong-Ryul Jung,
Sang Hwan Seo,
Se Chan Oh,
Young Ho Ban,
Xiaoxia Tan,
Jung Min Kim,
Jangwook Lee,
Duk Su Koh,
Hye Young Jung,
Young Jun Park,
Suk Ran Yoon,
Junsang Doh,
Sang Jun Ha,
Inpyo Choi,
Philip D. Greenberg
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-02697-x
Subject(s) - intracellular , microbiology and biotechnology , cd8 , t cell , cytotoxic t cell , gene knockdown , biology , chemistry , cytokine , antigen , cell culture , immune system , immunology , biochemistry , genetics , in vitro
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.