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

Research output: Contribution to journalArticle

4 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

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MicroRNAs
T-Lymphocytes
Cell Proliferation
Cytokines
Genes

All Science Journal Classification (ASJC) codes

  • General

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Kim, T. D., Jung, H. R., Seo, S. H., Oh, S. C., Ban, Y., Tan, X., ... 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
Kim, Tae Don ; Jung, Hong Ryul ; Seo, Sang Hwan ; Oh, Se Chan ; Ban, Youngho ; Tan, Xiaoxia ; Min Kim, Jung ; Hyun Lee, Sang ; Koh, Duk Su ; Jung, Haiyoung ; Park, Young Jun ; Ran Yoon, Suk ; Doh, Junsang ; Ha, Sang-Jun ; Choi, Inpyo ; Greenberg, Philip D. / MicroRNA-150 modulates intracellular Ca 2+ levels in naïve CD8+ T cells by targeting TMEM20. In: Scientific reports. 2017 ; Vol. 7, No. 1.
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title = "MicroRNA-150 modulates intracellular Ca 2+ levels in na{\"i}ve CD8+ T cells by targeting TMEM20",
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 na{\"i}ve CD8+ T cells, are not fully defined. Here, we showed that microRNA-150 (miR-150) controls intracellular Ca2+ levels in na{\"i}ve 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 na{\"i}ve 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 na{\"i}ve CD8+ T cells reduced intracellular Ca2+ levels. Our findings revealed that miR-150 play essential roles in controlling intracellular Ca2+ level and activation in na{\"i}ve CD8+ T cells, which suggest a mechanism to overcome anergy induction by the regulation of intracellular Ca2+ levels.",
author = "Kim, {Tae Don} and Jung, {Hong Ryul} and Seo, {Sang Hwan} and Oh, {Se Chan} and Youngho Ban and Xiaoxia Tan and {Min Kim}, Jung and {Hyun Lee}, Sang and Koh, {Duk Su} and Haiyoung Jung and Park, {Young Jun} and {Ran Yoon}, Suk and Junsang Doh and Sang-Jun Ha and Inpyo Choi and Greenberg, {Philip D.}",
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Kim, TD, Jung, HR, Seo, SH, Oh, SC, Ban, Y, Tan, X, Min Kim, J, Hyun Lee, S, Koh, DS, Jung, H, Park, YJ, Ran Yoon, S, Doh, J, Ha, S-J, Choi, I & Greenberg, PD 2017, 'MicroRNA-150 modulates intracellular Ca 2+ levels in naïve CD8+ T cells by targeting TMEM20', Scientific reports, vol. 7, no. 1, 2623. https://doi.org/10.1038/s41598-017-02697-x

MicroRNA-150 modulates intracellular Ca 2+ levels in naïve CD8+ T cells by targeting TMEM20. / Kim, Tae Don; Jung, Hong Ryul; Seo, Sang Hwan; Oh, Se Chan; Ban, Youngho; Tan, Xiaoxia; Min Kim, Jung; Hyun Lee, Sang; Koh, Duk Su; Jung, Haiyoung; Park, Young Jun; Ran Yoon, Suk; Doh, Junsang; Ha, Sang-Jun; Choi, Inpyo; Greenberg, Philip D.

In: Scientific reports, Vol. 7, No. 1, 2623, 01.12.2017.

Research output: Contribution to journalArticle

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T1 - MicroRNA-150 modulates intracellular Ca 2+ levels in naïve CD8+ T cells by targeting TMEM20

AU - Kim, Tae Don

AU - Jung, Hong Ryul

AU - Seo, Sang Hwan

AU - Oh, Se Chan

AU - Ban, Youngho

AU - Tan, Xiaoxia

AU - Min Kim, Jung

AU - Hyun Lee, Sang

AU - Koh, Duk Su

AU - Jung, Haiyoung

AU - Park, Young Jun

AU - Ran Yoon, Suk

AU - Doh, Junsang

AU - Ha, Sang-Jun

AU - Choi, Inpyo

AU - Greenberg, Philip D.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

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