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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Simvastatin promotes Th2-type responses through the induction of the chitinase family member Ym1 in dendritic cells
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Simvastatin promotes Th2-type responses through the induction of the chitinase family member Ym1 in dendritic cells

机译：辛伐他汀通过诱导几丁质酶家族成员Ym1在树突状细胞中促进Th2型反应

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摘要

Statins, best known for their lipid-lowering actions, also possess immunomodulatory properties. Recent studies have shown a Th2-biasing effect of statins, although the underlying mechanism has not been identified. in this study, we investigated whether simvastatin can exercise a Th2-promoting effect through modulation of function of dendritic cells (DCs) without direct interaction with CD4(+) T cells. Exposure of DCs to simvastatin induced the differentiation of a distinct subset of DCs characterized by a high expression of B220. These simvastatin-conditioned DCs up-regulated GATA-3 expression and down-regulated T-bet expression in cocultured CD4(+) T cells in the absence of additional simvastatin added to the coculture. The Th2-biased transcription factor profile induced by simvastatin-treated DCs also was accompanied by increased Th2 (IL-4, IL-5, and IL-13) and decreased Th1 (IFN-gamma) cytokine secretion from the T cells. The Th2-promoting effect of simvastatin was found to depend on the chitinase family member Ym1, known to be a lectin. Anti-Ym1 antibody abolished the Th2-promoting effect of simvastatin-treated DCs. Also, simvastatin was unable to augment Ym1 expression in DCs developed from STAT6(-/-) or IL-4R alpha(-/-) mice. Thus, modulation of Ym1 production by DCs identifies a previously undescribed mechanism of Th2 polarization by statin.
机译：他汀类药物以其降脂作用而闻名，还具有免疫调节特性。最近的研究表明他汀类药物具有Th2偏置作用，尽管其潜在机制尚未确定。在这项研究中，我们调查了辛伐他汀是否可以通过调节树突状细胞（DC）的功能而不与CD4（+）T细胞直接相互作用来行使Th2促进作用。将DC暴露于辛伐他汀诱导分化出DC的不同亚群，其以B220的高表达为特征。在没有其他辛伐他汀添加到共培养物中的情况下，这些辛伐他汀条件化的DC在共培养的CD4（+）T细胞中上调GATA-3表达和下调T-bet表达。辛伐他汀处理的DC诱导的Th2偏向转录因子谱还伴随着T2分泌的Th2（IL-4，IL-5和IL-13）增加和Th1（IFN-γ）细胞因子分泌减少。发现辛伐他汀的Th2促进作用取决于几丁质酶家族成员Ym1，后者被称为凝集素。抗Ym1抗体消除了辛伐他汀处理的DC的Th2促进作用。此外，辛伐他汀不能增加从STAT6（-/-）或IL-4R alpha（-/-）小鼠发育的DC中的Ym1表达。因此，DC对Ym1产生的调制识别了他汀类药物先前未描述的Th2极化机制。

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