5th Annual BMRP Investigator Meeting - Abstract

Therapeutic Approach Using Interleukin-22 in Experimental Colitis

Ken Sugimoto¹, Emiko Mizoguchi², Akira Andoh³, Atul K. Bhan¹ and Atsushi Mizoguchi<sup>1,a

1</sup>Department of Pathology and ²Department of Medicine, Massachusetts General Hospital and Harvard Medical School (Boston, U.S.A.) and ³Department of Medicine, Shiga University School of Medicine (Japan)

Expression of IL-22 that targets innate immunity is specifically induced in IBD patients.  However, the role of IL-22 in colitis has not yet been identified.  IL-22 expression was specifically elicited in the colonic CD4+ T cells under inflammatory conditions of experimental colitis models as well as IBD patients.  Interestingly, expression levels of IL-22 were significantly lower in the inflamed colon of UC as compared to CD patients.  In contrast, IL-22 receptor complex was constitutively expressed by the colonic epithelial cells (CEC) of UC and CD patients.  We established a new microinjection-based, lipid complex-mediated local gene delivery approach that induces local IL-22-overexpression that can specifically target the inflamed mucosa.  This IL-22 delivery specifically enhanced the STAT3 activation in the CEC and led to rapid attenuation of UC-like experimental chronic colitis.  Importantly, the IL-22 supplement significantly restored the goblet cell differentiation that is characteristically impaired in UC patients.  These findings suggest a therapeutic utilization of local IL-22 gene delivery to UC patients.

^aPrincipal Investigator