Dysregulated NOD2 predisposes SAMP1/YitFc mice to chronic intestinal inflammation

Daniele Corridoni, Tomohiro Kodani, Alexander Rodriguez-Palacios, Theresa T. Pizarro, Wei Xin, Kourtney P. Nickerson, Christine McDonald, Klaus F. Ley, Derek W. Abbott, Fabio Cominelli

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Nucleotide-binding oligomerization domain-containing 2 (NOD2) is an intracellular receptor that plays an essential role in innate immunity as a sensor of a component of the bacterial cell wall, muramyl dipeptide (MDP). Crohn's disease (CD)-associated NOD2 variants lead to defective innate immune responses, including decreased NF-κB activation and cytokine production. We report herein that SAMP1/YitFc (SAMP) mice, which develop spontaneous CD-like ileitis in the absence of NOD2 genetic mutations, fail to respond to MDP administration by displaying decreased innate cytokine production and dysregulated NOD2 signaling compared with parental AKR control mice. We show that, unlike in other mouse strains, in vivo administration of MDP does not prevent dextran sodium sulfate-induced colitis in SAMP mice and that the abnormal NOD2 response is specific to the hematopoietic cellular component. Moreover, we demonstrate that MDP fails to enhance intracellular bacterial killing in SAMP mice. These findings shed important light on the initiating molecular events underlying CD-like ileitis.

Original languageEnglish (US)
Pages (from-to)16999-17004
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number42
DOIs
StatePublished - Oct 15 2013
Externally publishedYes

ASJC Scopus subject areas

  • General

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