MicroRNA-150 modulates intracellular Ca2+ levels in naïve CD8+ T cells by targeting TMEM20
SCIE
SCOPUS
- Title
- MicroRNA-150 modulates intracellular Ca2+ levels in naïve CD8+ T cells by targeting TMEM20
- Authors
- DOH, JUNSANG; Tae-Don Kim; Hong-Ryul Jung; Sang-Hwan Se; Se-Chan Oh; Youngho Ban; Xiaoxia Tan; Jung Min Kim; Sang Hyun Lee; Duk-Su Koh; Haiyoung Jung; Young-Jun Park; Suk Ran Yoon; Inpyo Choi; Sang-Jun Ha; Philip D.Greenberg
- Date Issued
- 2017-06
- Publisher
- Nature Publishing Group
- Abstract
- Regulation of intracellular Ca2+ signaling is a major determinant of CD8+ T cell responsiveness, but the mechanisms underlying this regulation of Ca2+ levels, especially in naïve CD8+ T cells, are not fully defined. Here, we showed that microRNA-150 (miR-150) controls intracellular Ca2+ levels in naïve CD8+ T cells required for activation by suppressing TMEM20, a negative regulator of Ca2+ extrusion. miR-150 deficiency increased TMEM20 expression, which resulted in increased intracellular Ca2+ levels in naïve CD8+ T cells. The subsequent increase in Ca2+ 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 Ca2+ levels. Our findings revealed that miR-150 play essential roles in controlling intracellular Ca2+ level and activation in naïve CD8+ T cells, which suggest a mechanism to overcome anergy induction by the regulation of intracellular Ca2+ levels
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/39084
- DOI
- 10.1038/s41598-017-02697-x
- ISSN
- 2045-2322
- Article Type
- Article
- Citation
- Scientific Reports, vol. 7, page. 2623, 2017-06
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