赵立平+孟广勋等:NLRP3炎性小体突变,菌群与Treg联合确保肠道稳态

创作:女巫 审核:沈志勋 2018年04月08日
携带NLRP3炎性小体突变的Cryopyrin相关周期性综合征(CAPS)患者的皮肤、关节和眼睛中有自身免疫性炎症,但肠道中没有;
携带Nlrp3 R258W突变的CAPS模型小鼠的肠道维持内稳态,而且对实验性结肠炎和结直肠癌具有很强的抗性;
Nlrp3 R258W突变通过重塑肠道菌群,诱导增加调节性T细胞(Treg)以提高抗炎能力,;
Nlrp3 R258W突变仅在固有层单核吞噬细胞中直接增强IL-1β(而非IL-18)的分泌,进而增加局部抗菌肽促进菌群的重建。
延伸阅读
Nature Communications [IF:12.353]

Remodelling of the gut microbiota by hyperactive NLRP3 induces regulatory T cells to maintain homeostasis

通过超活化NLRP3诱导调节性T细胞维持内稳态以重建肠道菌群

2017-12-01, Article, 10.1038/s41467-017-01917-2more

Abstract:
Inflammasomes are involved in gut homeostasis and inflammatory pathologies, but the role of NLRP3 inflammasome in these processes is not well understood. Cryopyrin-associated periodic syndrome (CAPS) patients with NLRP3 mutations have autoinflammation in skin, joints, and eyes, but not in the intestine. Here we show that the intestines of CAPS model mice carrying an Nlrp3 R258W mutation maintain homeostasis in the gut. Additionally, such mice are strongly resistant to experimental colitis and colorectal cancer; this is mainly through a remodelled gut microbiota with enhanced anti-inflammatory capacity due to increased induction of regulatory T cells (Tregs). Mechanistically, NLRP3R258W functions exclusively in the lamina propria mononuclear phagocytes to directly enhance IL-1β but not IL-18 secretion. Increased IL-1β boosts local antimicrobial peptides to facilitate microbiota remodelling. Our data show that NLRP3R258W-induced remodelling of the gut microbiota, induces local Tregs to maintain homeostasis and compensate for otherwise-detrimental intestinal inflammation.

First Authors:
Xiaomin Yao

Correspondence Authors:
Liping Zhao,Guangxun Meng

All Authors:
Xiaomin Yao,Chenhong Zhang,Yue Xing,Guang Xue,Qianpeng Zhang,Fengwei Pan,Guojun Wu,Yingxin Hu,Qiuhong Guo,Ailing Lu,Xiaoming Zhang,Rongbin Zhou,Zhigang Tian,Benhua Zeng,Hong Wei,Warren Strober,Liping Zhao,Guangxun Meng