Role of Inflammasomes in Intestinal Inflammation and Crohn's Disease


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Abstract

Inflammasomes are multiprotein complexes that process procytokines into mature forms of interleukin 1β and interleukin 18 and induce pyroptotic cell death. Evidence linking NLRP3, NLRC4, and NLRP6 inflammasomes to intestinal inflammation is reviewed to provide a basis to understand how the innate immune system discriminates pathogenic bacteria from commensal bacteria and shapes microbial ecology. Inflammasomes have a direct and important role limiting colitis by directing effective immune responses against pathogenic bacterial infections in the intestine. Chronic granulomatous disease is presented to reveal a contrasting proinflammatory effect of inflammasomes. This pathogenic effect is unmasked in a state of immunodeficiency where bacterial growth is poorly controlled increasing inflammasome activity. The role of inflammasomes in inflammation associated with Crohn's disease and ulcerative colitis is discussed. Finally, mechanistic studies linking genetic polymorphisms in ATG16L and NOD2 to inflammasome activation provide a basis for new hypotheses to explain how genetic polymorphism associated with Crohn's disease modulate intestinal inflammation. A deeper understanding of the role of inflammasomes in intestinal inflammation is expected to identify new ways of treating inflammatory bowel disease.

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