Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cell. 2011 May 27;145(5):745-57. doi: 10.1016/j.cell.2011.04.022. Epub 2011 May 12.

NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis.

Author information

  • 1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.

Abstract

Inflammasomes 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.

Copyright © 2011 Elsevier Inc. All rights reserved.

Comment in

PMID:
21565393
[PubMed - indexed for MEDLINE]
PMCID:
PMC3140910
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central Icon for Faculty of 1000
    Loading ...
    Write to the Help Desk