CARD3 deficiency protects against colitis through reduced epithelial cell apoptosis.
BACKGROUND
Caspase activation and recruitment domain 3 (CARD3) is a 61-kDa protein kinase. Recent evidence shows the importance of CARD3 in the immune response and inflammatory diseases. To elucidate its impact on inflammatory bowel disease, we studied the effects of the loss of CARD3 in the acute dextran sodium sulfate-induced colitis.


METHODS
Colitis was induced by administration of dextran sodium sulfate to wild-type and CARD3 mice. Colon tissues were analyzed.


RESULTS
CARD3 mice were less susceptible to the development of colitis than wild-type controls as determined by weight loss, disease activity, colon histology, neutrophil infiltration, and cytokine expression. Reduced susceptibility of CARD3 mice to colitis was closely related to increased density of colonic epithelial cells relative to wild-type controls, which was because of decreased levels of apoptosis that resulted in enhanced epithelial barrier function. Finally, CARD3 levels were increased in intestinal tissue from patients with IBD.


CONCLUSIONS
These results imply a role for CARD3 as a positive regulator of intestinal epithelial cell apoptosis in the inflamed colon. Genetic loss of CARD3 is protective against colitis through decreased epithelial cell apoptosis and consequent enhancement of intestinal epithelial barrier function. Thus, targeted CARD3 inhibition may represent a new therapeutic approach in IBD.
Departments of *Gastroenterology, Key Laboratory of Hubei Province for Digestive System Disease, †Pathology, Renmin Hospital of Wuhan University, Wuhan, China; and ‡Cardiovascular Research Institute, Wuhan University, Wuhan, China.
Shi Jie
SJ
Yu
Ya
Y
Liu
Ya
Y
Deng
Xue Yong
XY
Zhu
Na
N
Zhan
Wei Guo
WG
Dong
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D003106:Colon / Q000166:cytology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000276:immunology
D016264:Dextran Sulfate; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506255:Ripk2 protein, mouse