4th Annual BMRP Investigator Meeting - Abstract
Therapeutic Approach Using Interleukin-22 in Experimental Colitis
Ken Sugimoto1, Atsuhiro Ogawa1, Yasuyo Shimomura1, Emiko Mizoguchi2, Atul K. Bhan1, Atsushi Mizoguchi1,a
1Department of Pathology, 2Department of Medicine, Massachusetts General Hospital, Harvard Medical School (Boston, Massachusetts, U.S.A.)
Intestinal epithelial homeostasis is constitutively maintained by various factors to prevent the development of inflammatory bowel disease (IBD). A recently identified IL-10 family cytokine, IL-22 has been demonstrated to specifically activate signal transducer and activator of transcription (STAT) 3 in innate cells such as epithelial cells, but not acquired immune cells. Through gene expression analysis, we have found that expression of IL-22 by T cells is specifically induced under intestinal inflammatory conditions observed in experimental colitis models as well as IBD patients. The receptors for IL-22 were constitutively expressed on the epithelial cells and macrophages, but not other cell types, in the colons of experimental colitis models and IBD patients. IL-22 significantly activated STAT3 in human colonic epithelial cell lines and freshly isolated colonic epithelial cells from mice. Inhibition of IL-22 activity in vivo by administration of neutralizing anti-IL-22 Abs enhanced the recovery from dextran sulfate sodium-induced acute intestinal inflammation. In addition, intestine-specific local delivery of IL-22 gene contributed to a rapid attenuation of chronic intestinal inflammation in TCRα knockout mice by restoring epithelial barrier function. Therefore, IL-22 is considered to be a new and effective therapeutic agent to improve the lives of patients with IBD.
aPrincipal Investigator