Atorvastatin promotes the expansion of myeloid-derived suppressor cells and attenuates murine colitis
Atorvastatin promotes the expansion of myeloid-derived suppressor cells and attenuates murine colitis
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DOI：
10.1111/imm.12662
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发表时间：
2016-12-01
期刊：
影响因子：
6.4
通讯作者：
Zhou, Jie
中科院分区：
文献类型：
--
作者：
Lei, Aihua;Yang, Qiong;Zhou, Jie
他汀类药物，作为降胆固醇药物被广泛使用，最近被广泛研究其对免疫系统的多效性作用，特别是其对自身免疫性和炎症性疾病的有益作用。然而，他汀类药物诱导免疫抑制的机制还远未了解。在这里，我们发现阿托伐他汀促进骨髓源性抑制细胞（MDSC）在体外和体内的扩增。阿托伐他汀衍生的MDSC通过产生一氧化氮抑制T细胞反应。添加甲羟戊酸（3-羟基-3-甲基戊二酰辅酶A还原酶的下游代谢产物）几乎完全消除了阿托伐他汀对MDSC的作用，表明涉及甲羟戊酸途径。沿着葡聚糖硫酸钠（DSS）诱导的小鼠急、慢性结肠炎的改善，我们观察到与DSS对照小鼠相比，脾和肠组织中MDSC水平均升高。更重要的是，阿托伐他汀衍生的MDSC的转移减弱了DSS急性结肠炎和慢性结肠炎的T细胞转移。因此，我们的数据表明，由他汀类药物诱导的MDSC的扩增可能对自身免疫性疾病产生有益的影响。总之，我们的研究为他汀类药物治疗炎症性肠病和其他自身免疫性疾病提供了一种新的潜在机制。
Statins, widely prescribed as cholesterol-lowering drugs, have recently been extensively studied for their pleiotropic effects on immune systems, especially their beneficial effects on autoimmune and inflammatory disorders. However, the mechanism of statin-induced immunosuppression is far from understood. Here, we found that atorvastatin promoted the expansion of myeloid-derived suppressor cells (MDSCs) both in vitro and in vivo. Atorvastatin-derived MDSCs suppressed T-cell responses by nitric oxide production. Addition of mevalonate, a downstream metabolite of 3-hydroxy-3-methylglutaryl coenzyme A reductase, almost completely abrogated the effect of atorvastatin on MDSCs, indicating that the mevalonate pathway was involved. Along with the amelioration of dextran sodium sulphate (DSS) -induced murine acute and chronic colitis, we observed a higher MDSC level both in spleen and intestine tissue compared with that from DSS control mice. More importantly, transfer of atorvastatin-derived MDSCs attenuated DSS acute colitis and T-cell transfer of chronic colitis. Hence, our data suggest that the expansion of MDSCs induced by statins may exert a beneficial effect on autoimmune diseases. In summary, our study provides a novel potential mechanism for statins-based treatment in inflammatory bowel disease and perhaps other autoimmune diseases.