Stigmasterol Restores the Balance of Treg/Th17 Cells by Activating the Butyrate-PPARγ Axis in Colitis.
Stigmasterol Restores the Balance of Treg/Th17 Cells by Activating the Butyrate-PPARγ Axis in Colitis.
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豆甾醇通过激活结肠炎中的丁酸-PPARγ 轴来恢复 Treg/Th17 细胞的平衡
DOI：
10.3389/fimmu.2021.741934
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发表时间：
2021
影响因子：
7.3
通讯作者：
Liu F
中科院分区：
文献类型：
--
作者：
Wen S;He L;Zhong Z;Zhao R;Weng S;Mi H;Liu F
炎症性肠病(IBD)是一种以肠道微生物区系失衡和调节性T(Treg)/T辅助T细胞(Th17)免疫失衡为特征的慢性炎症性疾病。豆甾醇，一种从植物中提取的甾醇，已经显示出抗炎作用。本研究旨在探讨豆甾醇对实验性结肠炎的治疗作用及其相关机制。在葡聚糖硫酸钠(DSS)诱导的结肠炎模型中，豆甾醇治疗恢复了Treg/Th17平衡，并改变了肠道微生物区系。移植接受豆甾醇治疗的小鼠的粪便微生物区系显著减轻了炎症。此外，豆甾醇处理促进了肠道微生物区系衍生的短链脂肪酸(SCFA)的产生，特别是丁酸盐。接下来，在Treg或Th17极化的条件下培养从IBD患者中分离出来的人幼稚的CD4+T细胞；补充丁酸可以增加Treg的分化，降低Th17细胞的分化。从机制上讲，丁酸盐可激活过氧化物酶体增殖物激活受体γ，重新编程能量代谢，从而促进Treg的分化，抑制Th17的分化。我们的结果表明，丁酸介导的PPARγ激活恢复了Treg/Th17细胞的平衡，这可能是豆甾醇减轻IBD的一个可能机制。
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with gut microbiota disequilibrium and regulatory T (Treg)/T helper 17 (Th17) immune imbalance. Stigmasterol, a plant-derived sterol, has shown anti-inflammatory effects. Our study aimed to identify the effects of stigmasterol on experimental colitis and the related mechanisms. Stigmasterol treatment restored the Treg/Th17 balance and altered the gut microbiota in a dextran sodium sulfate (DSS)-induced colitis model. Transplantation of the faecal microbiota of stigmasterol-treated mice significantly alleviated inflammation. Additionally, stigmasterol treatment enhanced the production of gut microbiota-derived short-chain fatty acids (SCFAs), particularly butyrate. Next, human naïve CD4+ T cells sorted from IBD patients were cultured under Treg- or Th17-polarizing conditions; butyrate supplementation increased the differentiation of Tregs and decreased Th17 cell differentiation. Mechanistically, butyrate activated peroxisome proliferator-activated receptor gamma (PPARγ) and reprogrammed energy metabolism, thereby promoting Treg differentiation and inhibiting Th17 differentiation. Our results demonstrate that butyrate-mediated PPARγ activation restores the balance of Treg/Th17 cells, and this may be a possible mechanism, by which stigmasterol attenuates IBD.