/   Home   /   Newsroom   /   Research News

NLRP3 Inflammasome Maintains Intestinal Homeostasis Through Modulating Gut Microbiota Induced Regulatory T Cells

Dec 07, 2017     Email"> PrintText Size

Inflammasomes are recently identified as cytosolic multi-protein complexes mediating specific proinflammatory signals such as maturation of IL-1β, IL-18 and processing Gasdermin D to provoke a specialized cell death, pyroptosis. They have been involved in gut homeostasis and inflammatory pathologies. Among many different inflammasomes, NLRP3 stands out for its complicated activation mechanisms, as well as its clinical significance.

In humans, dysregulation of inflammasome signalling by gain-of-function mutations in the coding region of NLRP3 results in a group of autoinflammatory diseases called cryopyrin-associated periodic syndromes. Mice carrying the homologous mutation in NLRP3 (NLRP3-R258W) show similar inflammation in skin and joints, but retained a healthy intestine, which indicates an unknown pathway for NLRP3-R258W to maintain gut homeostasis despite its hyperactivity.

In a recent study published in Nature Communications, MENG Guangxun's group at Institute Pasteur of Shanghai of Chinese Academy of Sciences, in cooperation with Prof. ZHAO Liping’s lab at Shanghai Jiaotong University, found that the NLRP3-R258W mice are not only healthy with their intestines, but also are with stronger resistance to dextran sulfate sodium (DSS) colitis and colorectal cancer.

The mutation led to a distinct gut microbiota with a sparingly interconnected co-abundance network, and nourished functional bacteria capable of inducing Tregs, which mediates neutralization of intestinal inflammation. Lack/inhibition of Tregs would lead to spontaneous colitis/loss of resistance to induced acute colitis.

Mechanistically, the microbiota was reshaped via increased local antimicrobial peptides boosted by the enhanced IL-1β but not IL-18 production from lamina propria mononuclear phagocytes containing mutated NLRP3.

This study for the first time revealed how NLRP3 functions in the intestine and how it cooperates with gut microbiota to harnessing Tregs to maintain intestinal homeostasis. It highlighted the importance of NLRP3’s contribution to the gut diseases and homeostasis, providing potential molecular targets for future treatments of intestinal disorders.

The study was funded by grants from Natural Science Foundation of China, National Key Basic Research programs of China, as well as Strategic priority program and International partnership program of Chinese Academy of Sciences.

 

Figure: Remodeling of the gut microbiota by hyperactive NLRP3 inflammasome induces regulatory T cells to maintain intestinal homeostasis (Image by the group)

Attachment:

(Editor: LIU Jia)

Contact

MENG Guangxun

Institut Pasteur of Shanghai

Phone:
E-mail: gxmeng@sibs.ac.cn

Related Articles

β-arrestin 1;NLRP3;NLRC4;inflammasome

Researchers Reveal Novel Function of β-arrestin1 in Regulation of Inflammasome Activity

Feb 03, 2015

The molecular activation mechanism of inflammasomes remains largely unknown in spite of their well-studied function in immune response and disease development. Researchers from the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences of ...

T cell;integrin b7 deficiency;immunity

Integrin β7 Required for Controlling Innate Immune-mediated Colitis

Aug 04, 2015

Dr. ZHANG Hailong and ZHENG Yajuan led by Professor CHEN Jianfeng from the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences demonstrate that integrin β7

Contact Us

Copyright © 2002 - 2017 Chinese Academy of Sciences