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Title: Genetic deletion of the bacterial sensor NOD2 improves murine Crohn’s disease-like ileitis independent of functional dysbiosis

Abstract

Although genetic polymorphisms in NOD2 (nucleotide-binding oligomerization domain-containing 2) have been associated with the pathogenesis of Crohn’s disease (CD), little is known regarding the role of wild-type (WT) NOD2 in the gut. To date, most murine studies addressing the role of WT Nod2 have been conducted using healthy (ileitis/colitis-free) mouse strains. Here, we evaluated the effects of Nod2 deletion in a murine model of spontaneous ileitis, i.e., the SAMP1Yit/Fc (SAMP) strain, which closely resembles CD. Remarkably, Nod2 deletion improved both chronic cobblestone ileitis (by 50% assessed, as the % of abnormal mucosa at 24 wks of age), as well as acute dextran sodium sulfate (DSS) colitis. Mechanistically, Th2 cytokine production and Th2-transcription factor activation (i.e., STAT6 phosphorylation) were reduced. Microbiologically, the effects of Nod2 deletion appeared independent of fecal microbiota composition and function, assessed by 16S rRNA and metatranscriptomics. Our findings indicate that pharmacological blockade of NOD2 signaling in humans could improve health in Th2-driven chronic intestinal inflammation.

Authors:
; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
National Institutes of Health (NIH); Crohn's and Colitis Foundation of America (CCFA)
OSTI Identifier:
1427533
DOE Contract Number:  
AC02-06CH11357
Resource Type:
Journal Article
Journal Name:
Mucosal Immunology
Additional Journal Information:
Journal Volume: 10; Journal Issue: 4; Journal ID: ISSN 1933-0219
Country of Publication:
United States
Language:
English

Citation Formats

Corridoni, D., Rodriguez-Palacios, A., Di Stefano, G., Di Martino, L., Antonopoulos, D. A., Chang, E. B., Arseneau, K. O., Pizarro, T. T., and Cominelli, F. Genetic deletion of the bacterial sensor NOD2 improves murine Crohn’s disease-like ileitis independent of functional dysbiosis. United States: N. p., 2016. Web. doi:10.1038/mi.2016.98.
Corridoni, D., Rodriguez-Palacios, A., Di Stefano, G., Di Martino, L., Antonopoulos, D. A., Chang, E. B., Arseneau, K. O., Pizarro, T. T., & Cominelli, F. Genetic deletion of the bacterial sensor NOD2 improves murine Crohn’s disease-like ileitis independent of functional dysbiosis. United States. doi:10.1038/mi.2016.98.
Corridoni, D., Rodriguez-Palacios, A., Di Stefano, G., Di Martino, L., Antonopoulos, D. A., Chang, E. B., Arseneau, K. O., Pizarro, T. T., and Cominelli, F. Wed . "Genetic deletion of the bacterial sensor NOD2 improves murine Crohn’s disease-like ileitis independent of functional dysbiosis". United States. doi:10.1038/mi.2016.98.
@article{osti_1427533,
title = {Genetic deletion of the bacterial sensor NOD2 improves murine Crohn’s disease-like ileitis independent of functional dysbiosis},
author = {Corridoni, D. and Rodriguez-Palacios, A. and Di Stefano, G. and Di Martino, L. and Antonopoulos, D. A. and Chang, E. B. and Arseneau, K. O. and Pizarro, T. T. and Cominelli, F.},
abstractNote = {Although genetic polymorphisms in NOD2 (nucleotide-binding oligomerization domain-containing 2) have been associated with the pathogenesis of Crohn’s disease (CD), little is known regarding the role of wild-type (WT) NOD2 in the gut. To date, most murine studies addressing the role of WT Nod2 have been conducted using healthy (ileitis/colitis-free) mouse strains. Here, we evaluated the effects of Nod2 deletion in a murine model of spontaneous ileitis, i.e., the SAMP1Yit/Fc (SAMP) strain, which closely resembles CD. Remarkably, Nod2 deletion improved both chronic cobblestone ileitis (by 50% assessed, as the % of abnormal mucosa at 24 wks of age), as well as acute dextran sodium sulfate (DSS) colitis. Mechanistically, Th2 cytokine production and Th2-transcription factor activation (i.e., STAT6 phosphorylation) were reduced. Microbiologically, the effects of Nod2 deletion appeared independent of fecal microbiota composition and function, assessed by 16S rRNA and metatranscriptomics. Our findings indicate that pharmacological blockade of NOD2 signaling in humans could improve health in Th2-driven chronic intestinal inflammation.},
doi = {10.1038/mi.2016.98},
journal = {Mucosal Immunology},
issn = {1933-0219},
number = 4,
volume = 10,
place = {United States},
year = {2016},
month = {11}
}

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