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 exp...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 gone 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 ofT 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 ofMFN2 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.展开更多
基金This study was supported by grants from the Natural Science Foundation of Zhejiang Province （No.LY13HI50006 and No. LY13H150004）, the National Natural Science Foundation （No. 81571937 and No. 81772112）, and the Key Construction Academic Subject （Medical Innovation） of Zhejiang Province （No. 11-CX26）.
文摘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 gone 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 ofT 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 ofMFN2 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.
