Role of the Ca2+-Calcineurin-Nuclear Factor of Activated T cell Pathway in Mitofusin-2-Mediated Immune Function of Jurkat Cells
| العنوان: | Role of the Ca2+-Calcineurin-Nuclear Factor of Activated T cell Pathway in Mitofusin-2-Mediated Immune Function of Jurkat Cells |
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| المؤلفون: | Yong-ming Yao, Xiu-Ping Xu, Yun-Long Jiang, Zong-sheng Wu, Guangju Zhao, Jun-Cong Li, Zhongqiu Lu, Guangliang Hong |
| المصدر: | Chinese Medical Journal Chinese Medical Journal, Vol 131, Iss 3, Pp 330-338 (2018) |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Calcineurin, Calcium, Jurkat Cells, Mitofusin-2 Protein, Nuclear Factor of Activated T cells, T-Lymphocytes, T cell, Calcineurin Inhibitors, lcsh:Medicine, Gene Expression, Lymphocyte Activation, Transfection, Jurkat cells, GTP Phosphohydrolases, Mitochondrial Proteins, 03 medical and health sciences, Immune system, medicine, Humans, RNA, Small Interfering, Cell Proliferation, Cell Nucleus, Innate immune system, NFATC Transcription Factors, Chemistry, lcsh:R, Lentivirus, NFAT, General Medicine, Acquired immune system, Molecular biology, Up-Regulation, 030104 developmental biology, medicine.anatomical_structure, Cytokines, Original Article, Signal Transduction |
| الوصف: | Background: Mitofusin-2 (MFN2), a well-known mitochondrial fusion protein, has been shown to participate in innate immunity, but its role in mediating adaptive immunity remains poorly characterized. In this study, we explored the potential role of MFN2 in mediating the immune function of T lymphocytes. Methods: We manipulated MFN2 gene expression in Jurkat cells via lentiviral transduction of MFN2 small interfering RNA (siRNA) or full-length MFN2. After transduction, the immune response and its underlying mechanism were determined in Jurkat cells. One-way analysis of variance and Student’s t-test were performed to determine the statistical significance between the groups. Results: Overexpression of MFN2 enhanced the immune response of T lymphocytes by upregulating Ca2+ (359.280 ± 10.130 vs. 266.940 ± 10.170, P = 0.000), calcineurin (0.513 ± 0.014 vs. 0.403 ± 0.020 nmol/L, P = 0.024), and nuclear factor of activated T cells (NFATs) activation (1.040 ± 0.086 vs. 0.700 ± 0.115, P = 0.005), whereas depletion of MFN2 impaired the immune function of T lymphocytes by downregulating Ca2+ (141.140 ± 14.670 vs. 267.060 ± 9.230, P = 0.000), calcineurin (0.054 ± 0.030 nmol/L vs. 0.404 ± 0.063 nmol/L, P = 0.000), and NFAT activation (0.500 ± 0.025 vs. 0.720 ± 0.061, P = 0.012). Furthermore, upregulated calcineurin partially reversed the negative effects of MFN2 siRNA on T cell-mediated immunity evidenced by elevations in T cell proliferation (1.120 ± 0.048 vs. 0.580 ± 0.078, P = 0.040), interleukin-2 (IL-2) production (473.300 ± 24.100 vs. 175.330 ± 12.900 pg/ml, P = 0.000), and the interferon-γ/IL-4 ratio (3.080 ± 0.156 vs. 0.953 ± 0.093, P = 0.000). Meanwhile, calcineurin activity inhibitor depleted the positive effects of overexpressed MFN2 on T cells function. Conclusions: Our findings suggest that MFN2 may regulate T cell immune functions primarily through the Ca2+-calcineurin-NFAT pathway. MFN2 may represent a potential therapeutic target for T cell immune dysfunction-related diseases. Key words: Calcineurin; Calcium; Jurkat Cells; Mitofusin-2 Protein; Nuclear Factor of Activated T cells |
| تدمد: | 0366-6999 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1bb88da67a71272d6e3cbfbfd3683053Test https://doi.org/10.4103/0366-6999.223855Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1bb88da67a71272d6e3cbfbfd3683053 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 03666999 |
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