| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2036372 | Cell | 2011 | 13 Pages |
SummaryInflammasomes are multiprotein complexes that function as sensors of endogenous or exogenous damage-associated molecular patterns. Here, we show that deficiency of NLRP6 in mouse colonic epithelial cells results in reduced IL-18 levels and altered fecal microbiota characterized by expanded representation of the bacterial phyla Bacteroidetes (Prevotellaceae) and TM7. NLRP6 inflammasome-deficient mice were characterized by spontaneous intestinal hyperplasia, inflammatory cell recruitment, and exacerbation of chemical colitis induced by exposure to dextran sodium sulfate (DSS). Cross-fostering and cohousing experiments revealed that the colitogenic activity of this microbiota is transferable to neonatal or adult wild-type mice, leading to exacerbation of DSS colitis via induction of the cytokine, CCL5. Antibiotic treatment and electron microscopy studies further supported the role of Prevotellaceae as a key representative of this microbiota-associated phenotype. Altogether, perturbations in this inflammasome pathway, including NLRP6, ASC, caspase-1, and IL-18, may constitute a predisposing or initiating event in some cases of human IBD.PaperClip To listen to this audio, enable JavaScript on your browser. However, you can download and play the audio by clicking on the icon belowHelp with MP3 filesOptionsDownload audio (4691 K)
Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (453 K)Download as PowerPoint slideHighlights► NLRP6 inflammasome in colonic epithelium regulates gut microflora ► NLRP6−/− mice exhibit dysbiosis, with expansion of Prevotellaceae and TM7 ► Dysbiosis results in transmissible autoinflammation ► Microflora-induced inflammation is caused by epithelial CCL5 induction
