Lee Young-Sun, Eun Hyuk Soo, Kim So Yeon, Jeong Jong-Min, Seo Wonhyo, Byun Jin-Seok, Jeong Won-Il, Yi Hyon-Seung
Department of Internal Medicine, Korea University College of Medicine, Seoul 136-705, Republic of Korea.
Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 305-764, Republic of Korea.
Sci Rep. 2016 Jul 28;6:30656. doi: 10.1038/srep30656.
Emerging evidence revealed that diabetes induces abnormal immune responses that result in serious complications in organs. However, the effect of hyperglycemia on hepatic immunity remains obscure. We evaluated the population and function of hepatic immune cells in streptozotocin (STZ)-induced hyperglycemic mice. CC chemokine receptor 2 (CCR2)-knockout mice and mice with a depletion of regulatory T cells (DEREG) were used to investigate the migration and role of regulatory T cells (Tregs) in hyperglycemic mice. The inflammatory cytokines and hepatic transaminase levels were significantly increased in the hyperglycemic mice. The population and number of infiltrating monocytes, granulocytes, and Tregs were enhanced in the livers of the hyperglycemic mice. Hepatic monocytes other than macrophages showed the increased expression of inflammatory cytokines and chemokines in the hyperglycemic mice. The CCR2 knockout and DEREG chimeric mice exhibited increased populations of activated T cells and neutrophils compared to the WT chimeric mice, which promoted hepatic inflammation in the hyperglycemic mice. The migration of CCR2 knockout Tregs into the liver was significantly reduced compared to the WT Tregs. We demonstrated that hyperglycemia contributes to increase in infiltrating monocytes and Tregs, which are associated with hepatic immune dysfunction in mice. CCR2-mediated migration of Tregs regulates hyperglycemia-induced hepatic inflammation.
新出现的证据表明，糖尿病会引发异常免疫反应，导致器官出现严重并发症。然而，高血糖对肝脏免疫的影响仍不清楚。我们评估了链脲佐菌素（STZ）诱导的高血糖小鼠肝脏免疫细胞的数量和功能。利用CC趋化因子受体2（CCR2）基因敲除小鼠和调节性T细胞耗竭的小鼠（DEREG）来研究调节性T细胞（Tregs）在高血糖小鼠中的迁移和作用。高血糖小鼠的炎性细胞因子和肝转氨酶水平显著升高。高血糖小鼠肝脏中浸润的单核细胞、粒细胞和Tregs的数量和比例均增加。除巨噬细胞外，高血糖小鼠肝脏中的单核细胞炎性细胞因子和趋化因子表达增加。与野生型嵌合小鼠相比，CCR2基因敲除和DEREG嵌合小鼠的活化T细胞和中性粒细胞数量增加，这促进了高血糖小鼠的肝脏炎症。与野生型Tregs相比，CCR2基因敲除的Tregs向肝脏的迁移显著减少。我们证明，高血糖会导致浸润的单核细胞和Tregs增加，这与小鼠肝脏免疫功能障碍有关。CCR2介导的Tregs迁移调节高血糖诱导的肝脏炎症。
