Inflammasome, Inflammation, and Tissue Homeostasis

• Published in: Trends in molecular medicine 2018-03, Vol.24 (3), p.304-318
• Main Authors: Rathinam, Vijay A.K., Chan, Francis Ka-Ming
• Format: Article
• Language: English
• Subjects: ASC; CASPASE-1; CASPASE-8; gasdermin; IL-18; IL-1β; intestine; wound healing
• ISSN: 1471-4914; 1471-499X
• DOI: 10.1016/j.molmed.2018.01.004

Organismal fitness demands proper response to neutralize the threat from infection or injury. At the mammalian intestinal epithelium barrier, the inflammasome coordinates an elaborate tissue repair response marked by the induction of antimicrobial peptides, wound-healing cytokines, and reparative proliferation of epithelial stem cells. The inflammasome in myeloid and intestinal epithelial compartments exerts these effects in part through maintenance of a healthy microbiota. Disease-associated mutations and elevated expression of certain inflammasome sensors have been identified. In many cases, inhibition of inflammasome activity has dramatic effects on disease outcome in mouse models of experimental colitis. Here, we discuss recent studies on the role of distinct inflammasome sensors in intestinal homeostasis and how this knowledge may be translated into a therapeutic setting. Tissue homeostasis in the intestine requires the coordinate action between immune effectors, stromal cells and the commensal microbiota. Distinct inflammasome sensors mediate the crosstalk between immune effectors, intestinal epithelial cells, and the microbiota to maintain intestinal homeostasis. The cytokines IL-1β and IL-18 have key functions in the maintenance of homeostatic balance in the intestine. Whether cytokines promote or inhibit pathological inflammation is determined by the strength and duration of their activity.