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首页> 外文期刊>Cellular Physiology and Biochemistry >Farnesoid X Receptor in Mice Prevents Severe Liver Immunopathology During Lymphocytic Choriomeningitis Virus Infection
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Farnesoid X Receptor in Mice Prevents Severe Liver Immunopathology During Lymphocytic Choriomeningitis Virus Infection

机译：小鼠中的Farnesoid X受体可预防淋巴细胞性脉络膜脑膜炎病毒感染期间的严重肝免疫病理学

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>Background: Bile acids (BAs) are steroid molecules that are synthesized in the liver. In addition to their important role as a surfactant in solubilizing lipids and promoting the absorption of lipids in the gastrointestinal tract, they act as inflammagens. The role of BAs and their receptor farnesoid X receptor (FXR) during viral infection has not been studied in detail. Methods: By using FXR-deficient mice, we investigated the role of bile acid receptor FXR during infection with lymphocytic choriomeningitis virus (LCMV). The importance of FXR in inducing IFN-I and monocytes proliferation were investigated and viral titers and T cell exhaustion were analyzed at different time points. Results: This study shows that controlled levels of BAs activate FXR in hepatocytes and FXR in response upregulates the production of type I interferon. In turn, FXR maintains BAs within a balanced range to inhibit their toxic effects. The absence of FXR results in high levels of BAs, which inhibit the proliferation of monocytes and result in a defect in viral elimination, consequently leading to T cell exhaustion. Conclusion: We found that FXR contributes to IFN-I production in hepatocytes and balances BA levels to inhibit their toxic effects on monocytes.
机译：> 背景： 胆汁酸（BAs）是在肝脏中合成的类固醇分子。除了在溶解脂质和促进脂质在胃肠道中吸收方面作为表面活性剂的重要作用外，它们还起炎症作用。尚未详细研究BAs及其受体法呢类X受体（FXR）在病毒感染过程中的作用。 方法： 通过使用FXR缺陷型小鼠，我们研究了胆汁酸受体FXR在淋巴细胞性脉络膜脑膜炎病毒（LCMV）感染过程中的作用。研究了FXR在诱导IFN-I和单核细胞增殖中的重要性，并在不同时间点分析了病毒滴度和T细胞衰竭。 结果： 这项研究表明，受控水平的BA激活了肝细胞中的FXR，而FXR在响应中上调了I型干扰素的产生。反过来，FXR将BA保持在平衡范围内，以抑制其毒性作用。缺少FXR会导致高水平的BA，从而抑制单核细胞的增殖并导致病毒消除缺陷，从而导致T细胞衰竭。 结论： 我们发现FXR有助于肝细胞中IFN-I的产生，并平衡BA水平以抑制其对单核细胞的毒性作用。

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