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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Peroxisome proliferator-activated receptor (PPAR)α and -γ regulate IFN_γ and IL-17A production by human T cells in a sex-specific way
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Peroxisome proliferator-activated receptor (PPAR)α and -γ regulate IFN_γ and IL-17A production by human T cells in a sex-specific way

机译:过氧化物酶体增殖物激活受体(PPAR)α和-γ以性别特异性方式调节人T细胞产生的IFN_γ和IL-17A

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摘要

Women develop certain autoimmune diseases more often than men. It has been hypothesized that this may relate to the development of more robust T-helper (Th)1 responses in women. To test whether women exhibit a Th1 bias, we isolated naive cluster of differentiation (CD)4~+ T cells from peripheral blood of healthy women and men and measured the proliferation and cytokine production by these cells in response to submaximal amounts of anti-CD3 and anti-CD28. We observed that CD4~+ T cells from women produced higher levels of IFNγ as well as tended to proliferate more than male CD4~+ T cells. Intriguingly, male CD4~+ T cells instead had a predilection toward IL-17A production. This sex dichotomy in Th cytokine production was found to be even more striking in the Swiss/Jackson Laboratory (SJL) mouse. Studies in mice and humans indicated that the sexual dimorphism in Th1 and Th17 cytokine production was dependent on the androgen status and the T-cell expression of peroxisome proliferator activated receptor (PPAR)a and PPARγ. Androgens increased PPARa and decreased PPARγ expression by human CD4~+ T cells. PPARα siRNA-mediated knockdown had the effect of increasing IFNy by male CD4~+ T cells, while transfection of CD4~+ T cells with PPARγ siRNAs increased IL-17A production uniquely by female T cells. Together, our observations indicate that human T cells exhibit a sex difference in the production of IFNγ and IL-17A that may be driven by expressions of PPARα and PPARγ.
机译:女性比男性更容易患某些自身免疫性疾病。据推测,这可能与女性中更有效的T-helper(Th)1反应的发展有关。为了测试女性是否表现出Th1偏倚,我们从健康女性和男性的外周血中分离了幼稚的分化(CD)4〜+ T细胞簇,并测量了这些细胞对次最大量抗CD3的反应增殖和细胞因子产生。和抗CD28。我们观察到女性的CD4〜+ T细胞比男性的CD4〜+ T细胞产生更高水平的IFNγ,并且倾向于增殖更多。有趣的是,雄性CD4〜+ T细胞更倾向于IL-17A的产生。在瑞士/杰克逊实验室(SJL)小鼠中发现Th细胞因子产生的这种性别二分法更为显着。在小鼠和人类中的研究表明,Th1和Th17细胞因子产生的性二态性取决于过氧化物酶体增殖物激活受体(PPAR)a和PPARγ的雄激素状态和T细胞表达。雄激素会增加人CD4〜+ T细胞的PPARa表达并降低PPARγ表达。 PPARαsiRNA介导的敲低具有增加雄性CD4〜+ T细胞的IFNγ的作用,而用PPARγsiRNA转染CD4〜+ T细胞则增加了雌性T细胞的IL-17A产生。总之,我们的观察结果表明,人类T细胞在IFNγ和IL-17A产生中表现出性别差异,这可能是由PPARα和PPARγ的表达驱动的。

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  • 作者单位

    Department of Immunology, University of Toronto, Toronto, ON, Canada M5S 1A8,Division of Cell and Molecular Biology, University Health Network,Toronto, ON, Canada M5G 2M1;

    Division of Cell and Molecular Biology, University Health Network,Toronto, ON, Canada M5G 2M1;

    Division of Cell and Molecular Biology, University Health Network,Toronto, ON, Canada M5G 2M1;

    Neuroimmunology Research Unit, Center for Excellence in Neuromics, Centre Hospitaller de I'Universite de Montreal-Notre-Dame Hospital, Universite de Montreal, Montreal, QC, Canada H2L 4M1;

    Department of Immunology, University of Toronto, Toronto, ON, Canada M5S 1A8,Division of Cardiology, University Health Network, Toronto, ON, Canada M5G 2M1;

    Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305-5316;

    Division of Cardiology, University Health Network, Toronto, ON, Canada M5G 2M1,institute for Genetics, University of Cologne, 50674 Cologne, Germany;

    Department of Obstetrics and Gynecology, Women's and Children's Hospital, University of Southern California, Los Angeles, CA 90033;

    Neuroimmunology Research Unit, Center for Excellence in Neuromics, Centre Hospitaller de I'Universite de Montreal-Notre-Dame Hospital, Universite de Montreal, Montreal, QC, Canada H2L 4M1,Multiple Sclerosis Clinic, Department of Neurology, Centre Hospitalier de I'Universite de Montreal-Notre-Dame Hospital, Montreal, QC, Canada H2L4M1;

    Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305-5316;

    Department of Immunology, University of Toronto, Toronto, ON, Canada M5S 1A8,Division of Cell and Molecular Biology, University Health Network,Toronto, ON, Canada M5G 2M1,Women's College Research Institute, Toronto, ON, Canada, M5S 1B2;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    autoimmunity; cytokines; experimenta; autoimmune encephalomyelitis; gender; nuclear receptor;

    机译:自身免疫细胞因子实验自身免疫性脑脊髓炎;性别;核受体;

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