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

Tae Don Kim, Hong Ryul Jung, Sang Hwan Seo, Se Chan Oh, Youngho Ban, Xiaoxia Tan, Jung Min Kim, Sang Hyun Lee, Duk Su Koh, Haiyoung Jung, Young Jun Park, Suk Ran Yoon, Junsang Doh, Sang Jun Ha, Inpyo Choi, Philip D. Greenberg

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6 Citations (Scopus)

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.

Original languageEnglish
Article number2623
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

All Science Journal Classification (ASJC) codes

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    Kim, T. D., Jung, H. R., Seo, S. H., Oh, S. C., Ban, Y., Tan, X., Min Kim, J., Hyun Lee, S., Koh, D. S., Jung, H., Park, Y. J., Ran Yoon, S., Doh, J., Ha, S. J., Choi, I., & Greenberg, P. D. (2017). MicroRNA-150 modulates intracellular Ca 2+ levels in naïve CD8+ T cells by targeting TMEM20. Scientific reports, 7(1), [2623]. https://doi.org/10.1038/s41598-017-02697-x