NOD2 mutation and mice: no Crohn's disease but many lessons to learn.
Many patients with ileal Crohn's disease, a chronic intestinal inflammation, carry mutations in the gene encoding NOD2 (CARD15), but the mechanistic details of how this mutation leads to disease are not fully understood. NOD2 is expressed in antigen-presenting cells and Paneth cells, which are secretory epithelial cells of the small intestine. Two complementary studies using genetically engineered murine models help to explain the association of NOD2 malfunction and mucosal disease. One study observes a dysregulation of proinflammatory responses, suggesting that the most common NOD2 mutation in humans results in a gain of function. The other study determined that NOD2-null mutations impair the Paneth-cell antimicrobial response, which is consistent with recent findings in humans. Together, these studies fuel optimism that new therapeutic directions might emerge to better treat this severe mucosal disease.
Wehkamp
Jan
J
University of California-Davis School of Medicine, Department of Microbiology and Immunology, 1 Shield Avenue, Tupper Hall 3146, Davis, CA 95616, USA. jwehkamp@ucdavis.edu
Stange
Eduard F
EF
D000818:Animals; D001424:Bacterial Infections / Q000628:therapy; D003424:Crohn Disease / Q000235:genetics* / Q000382:microbiology; D006801:Humans; D007422:Intestines / Q000382:microbiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein; D019879:Paneth Cells / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse