MicroRNA-150 modulates intracellular Ca 2+ levels in naïve 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 naïve CD8+ T cells, are not fully defined. Here, we showed that microRNA-150 (miR-150) controls intracellular Ca2+ lev...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/30c9bb05268048c4babaae073c535db7
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spelling	oai:doaj.org-article:30c9bb05268048c4babaae073c535db72021-12-02T16:06:49ZMicroRNA-150 modulates intracellular Ca 2+ levels in naïve CD8+ T cells by targeting TMEM2010.1038/s41598-017-02697-x2045-2322https://doaj.org/article/30c9bb05268048c4babaae073c535db72017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02697-xhttps://doaj.org/toc/2045-2322Abstract 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.Tae-Don KimHong-Ryul JungSang-Hwan SeoSe-Chan OhYoungho BanXiaoxia TanJung Min KimSang Hyun LeeDuk-Su KohHaiyoung JungYoung-Jun ParkSuk Ran YoonJunsang DohSang-Jun HaInpyo ChoiPhilip D. GreenbergNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 MicroRNA-150 modulates intracellular Ca 2+ levels in naïve CD8+ T cells by targeting TMEM20
description	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.
format	article
author	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
author_facet	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
author_sort	Tae-Don Kim
title	MicroRNA-150 modulates intracellular Ca 2+ levels in naïve CD8+ T cells by targeting TMEM20
title_short	MicroRNA-150 modulates intracellular Ca 2+ levels in naïve CD8+ T cells by targeting TMEM20
title_full	MicroRNA-150 modulates intracellular Ca 2+ levels in naïve CD8+ T cells by targeting TMEM20
title_fullStr	MicroRNA-150 modulates intracellular Ca 2+ levels in naïve CD8+ T cells by targeting TMEM20
title_full_unstemmed	MicroRNA-150 modulates intracellular Ca 2+ levels in naïve CD8+ T cells by targeting TMEM20
title_sort	microrna-150 modulates intracellular ca 2+ levels in naïve cd8+ t cells by targeting tmem20
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/30c9bb05268048c4babaae073c535db7
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MicroRNA-150 modulates intracellular Ca 2+ levels in naïve CD8+ T cells by targeting TMEM20

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