@article{WU2023, 
author = {Tianyu WU and Yalan SONG and Jingfeng WU and Zhiyuan ZHENG and Ning ZHANG and Zimo ZHOU and Hong TANG and Fengchao WANG and Wensheng CHEN},
title = {Overexpression of IL22 by adeno-associated virus effectively ameliorates dextran sulfate sodium-induced colitis in mice},
year = {2023},
journal = {Journal of Army Medical University},
volume = {45},
number = {19},
pages = {1995-2006},
keywords = {IL22, adeno-associated virus, inflammatory bowel disease, dextran sulfate sodium, Jak/Stat3 pathway},
url = {https://www.sciopen.com/article/10.16016/j.2097-0927.202307121},
doi = {10.16016/j.2097-0927.202307121},
abstract = {ObjectiveTo investigate the effects of interleukin22（IL22）in acute colitis induced by dextran sulfate sodium salt（DSS）in mice and its underlying mechanism.MethodsThree IL22 knockout mice（IL22-/-）and 3 control mice（IL22+/+）of 8-week-old males were subjected from the same litter, and then had free-choice drinking of 2.5% DSS water for 6 d followed by normal water for 2 d to construct a mouse model of acute colitis. The changes in body mass weight and disease activity index（DAI）were measured and calculated. After the intervention of 8 d, mouse enteroscopy was performed, and the length of colon and the organ index of major immune organs were measured in both groups. Protein levels of pro-inflammatory cytokines, such as IL1α, IL1β, IL6 and TNFα were detected by Western blotting. Adeno-associated virus（AAV）transfection model was established in 8-week-old male C57BL/6 mice, which were then treated by 2.5%DSS drinking. The mice were randomly divided into PBS group（n=5）, AAV-mock+DSS group（n=5）and AAV-IL22+DSS group（n=5）. The expression levels of colonic closed small loop protein 1（ZO-1）and calcium adhesion protein（E-claudin）in different groups were detected by immunofluorescence assay. The protein levels of IL22, Occludin, Stat3 and p-Stat3 were detected by Western blotting.ResultsCompared with the IL22+/+ group, the mice in the IL22-/- group had significantly decreased body weight on day 8（P<0.05）, obviously increased DAI score（P<0.01）, endoscopy score（P<0.05）and pathological score（P<0.01）after DSS induction, and notable up-regulation of pro-inflammatory cytokines including IL1α, IL1β, cleaved-IL1β, IL6, and TNFα in the colon tissues（P<0.05）. While AAV-IL22 transfection reversed DSS-induced colitis. Significantly reduced inflammation in colonic tissues（P<0.05）, enhanced E-claudin expression（P<0.05）and up-regulation of p-Stat3 and Occludin（P<0.01）were observed in the AAV-IL22+DSS group than the AAV-mock+DSS group.ConclusionIL22 deficiency aggravates DSS-induced colitis in mice, and its overexpression by AAV-IL22 alleviates DSS enteritis by enhancing colonic tight junction proteins and reducing inflammatory infiltration, which may be related to the activation of Jak/Stat3 pathway.}
}