3rd Annual BMRP Investigator Meeting - Abstract

A Role of Innate Immunity in the Pathogenesis of Inflammatory Bowel Disease

Koichi Kobayashi^1,a, Mathias Chamaillard^2,3, Yasunori Ogura⁴, Liming Hao⁵, Octavian Henegariu⁴, Naohiro Inohara², Gabriel Nuñez^2,3 and Richard A. Flavell<sup>4,6

1</sup>Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute and Harvard Medical School (Boston, Massachusetts, U.S.A.); ²Department of Pathology and ³Comprehensive Cancer Center, The University of Michigan Medical School (Ann Arbor, Michigan, U.S.A.); ⁴Section of Immunobiology, ⁵Department of Pathology and ⁶the Howard Hughes Medical Institute, Yale University School of Medicine (New Haven, Connecticut, U.S.A.)

The gene encoding the Nod2 protein is frequently mutated in Crohn’s disease (CD) patients, although the physiological function of Nod2 itself in the intestine remains elusive. To reveal the function of Nod2, we generated Nod2-deficient mice using mouse embryonic cells.  Nod2 mice have been born at the expected rate and appeared healthy. There was no inflammation in intestinal tract observed by H&E stained sections. Protective immunity mediated by Nod2 recognition of bacterial muramyl dipeptide (MDP) is abolished in Nod2-deficient mice in vitro and in vivo.  These animals are susceptible to bacterial infection via the oral route, but not through intravenous or peritoneal delivery. Nod2 is required for expression of a subgroup of intestinal anti-microbial peptides, known as cryptdins.  Nod2, thus, represents a critical regulator of bacterial immunity within the intestine.