摘要
肠道组织高表达表观遗传调控因子沉默信息调节因子(silent information regulator 6, SIRT6),在UC患者及动物模型的结肠组织中,SIRT6的表达水平显著下调。关于SIRT6在调控肠道免疫平衡中的作用尚不清楚。新近发现的Ⅲ型固有淋巴细胞(group 3 innate lymphoid cell, ILC3)主要分布于肠道,对维持肠道免疫稳态非常重要。为探讨ILC3中SIRT6在结肠炎发生发展中的作用,应用FCM检测小鼠肠道组织中固有淋巴细胞(innate lymphoid cell, ILC)亚群比例,FACS分选ILC,荧光定量PCR检测Sirt6表达。结果发现,Sirt6在ILC3中有较高的表达丰度。运用Cre-loxp系统建立ILC3条件性敲除Sirt6小鼠模型,观察基础状态以及葡聚糖硫酸钠(dextran sulfate sodium salt, DSS)诱导性肠炎模型中小鼠的表型变化。结果显示,Sirt6在ILC3中缺失并不影响基础状态下小鼠的生长发育和肠道结构,但能显著提高小鼠对DSS诱导性结肠炎的抵抗能力。以上结果提示SIRT6通过调控ILC3影响肠炎的发生发展过程。
SIRT6 is a critical epigenetic regulator and is highly expressed in intestine tissues. Studies have demonstrated that SIRT6 is significantly downregulated in both human UC patients and DSS-induced mouse colitis model. Group 3 innate lymphoid cell(ILC3) is newly discovered immune cells in the gut and plays an important role in gut immunity. However, the role of SIRT6 in regulating ILC3 function and gut immunity remains unclear. In this study, we found that Sirt6 was highly expressed in ILC3. To further investigate whether Sirt6 in ILC3 would affect the development of colitis, FCM was used to test the ILC subgroup percentage in mouse gut and Sirt6 was quantitated by Q-PCR. The results showed that Sirt6 was highly expressed in ILC3. We generated ILC3-specific Sirt6 KO mice using Cre-loxp system. We checked the phenotype of WT mice vs KO mice in steady state and in DSS-induced colitis model. The results showed that ILC3-specific Sirt6 KO mice had no difference during development under steady state, but they were more resistant to DSS-induced colitis. In conclusion, SIRT6 plays an important role in the pathogenesis of colitis in the DDS-induced mouse colitis model by regulating ILC3.
作者
苏小惠
沈蕾
SU Xiao-hui;SHEN Lei(Shanghai Institute of Immunology,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)
出处
《现代免疫学》
CAS
CSCD
北大核心
2019年第5期370-377,共8页
Current Immunology
