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- Title
IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis.
- Authors
Sugimoto, Ken; Ogawa, Atsuhiro; Mizoguchi, Emiko; Shimomura, Yasuyo; Andoh, Akira; Bhan, Atul K.; Blumberg, Richard S.; Xavier, Ramnik J.; Mizoguchi, Atsushi
- Abstract
Expression of IL-22 is induced in several human inflammatory conditions, including inflammatory bowel disease (IBD). Expression of the IL-22 receptor is restricted to innate immune cells; however, the role of IL-22 in colitis has not yet been defined. We developed what we believe to be a novel microinjection-based local gene-delivery system that is capable of targeting the inflamed intestine. Using this approach, we demonstrated a therapeutic potency for IL-22-mediated activation of the innate immune pathway in a mouse model of Th2-mediated colitis that induces disease with characteristics similar to that of IBD ulcerative colitis (UC). IL-22 gene delivery enhanced STAT3 activation specifically within colonic epithelial cells and induced both STAT3-dependent expression of mucus-associated molecules and restitution of mucus-producing goblet cells. Importantly, IL-22 gene delivery led to rapid amelioration of local intestinal inflammation. The amelioration of disease by IL-22 was mediated by enhanced mucus production. In addition, local gene delivery was used to inhibit IL-22 activity through overexpression of IL-22-binding protein. Treatment with IL-22-binding protein suppressed goblet cell restitution during the recovery phase of a dextran sulfate sodium-induced model of acute colitis. These data demonstrate what we believe to be a novel function for IL-22 in the intestine and suggest the potency of a local IL-22 gene-delivery system for treating UC.
- Subjects
ULCERATIVE colitis; MUCUS; EPITHELIAL cells; CARRIER proteins; EXOCRINE secretions; CROHN'S disease; BLOOD plasma substitutes; EXFOLIATIVE cytology; COLITIS treatment; ANIMAL experimentation; BIOLOGICAL models; COMPARATIVE studies; GENE therapy; GENETIC techniques; INTERLEUKINS; RESEARCH methodology; MEDICAL cooperation; MICE; RESEARCH; T cells; TRANSFERASES; EVALUATION research
- Publication
Journal of Clinical Investigation, 2008, Vol 118, Issue 2, p534
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI33194