The NLRP1 inflammasome attenuates colitis and colitis-associated tumorigenesis.

摘要: Nucleotide-binding domain and leucine-rich repeat (NLR) proteins are a diverse family of pattern recognition receptors that essential mediators inflammation host defense in the gastrointestinal system. Recent studies have identified subgroup inflammasome forming NLRs modulate mucosal immune response during inflammatory bowel disease (IBD) colitis associated tumorigenesis. To better elucidate contribution NLR members IBD cancer, we conducted retrospective analysis gene expression metadata from human patients. These data revealed NLRP1, an NLR, was significantly dysregulated colon cancer. characterize function NLRP1 pathogenesis, used Nlrp1b(-/-) mice colitis-associated cancer models. In this paper, report attenuates demonstrated significant increases morbidity, inflammation, tumorigenesis compared with wild-type animals. Similar to previously reported for related NLRs, increased tumor burden correlated attenuated levels IL-1β IL-18. Further mechanistic using bone marrow reconstitution experiments pathogenesis nonhematopoietic-derived cells suggests functions epithelial cell compartment attenuate Taken together, these identify as mediator findings consistent model whereby multiple inflammasomes pathobiology through modulating IL-18 colon.