IL-37b gene transfer enhances the therapeutic efficacy of mesenchumal stromal cells in DSS- induced colitis mice  

作　　者：Wei-qiang WANG Kui DONG Lu ZHOU Guo-hui JIAO Cong-zhong ZHU Wen-wen LI Gang YU Wan-tong WU Song CHEN Zhi-na SUN Yu-ming WANG Wen-tian LIU Jie ZHANG Bang-mao WANG Xiao-ming FENG 

机构地区：[1]Departments ofGastroenterology and Hepatology and Tianjin Medical University, Tianjin 300052 [2]Departments of Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, [3]State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China

出　　处：《Acta Pharmacologica Sinica》2015年第11期1377-1387,共11页中国药理学报（英文版）

基　　金：Acknowledgements This work was supported by the National Basic Research Pro-gram of China （2013CB966904 and 2015CB964402）, the National Natural Science Foundation of China （81200282, 81273217, 81322007, 81170007, and 81370104）, and the Recruitment Program of Global Youth Experts.

摘　　要：Aim： To investigate whether the transfer of the IL-37b gene, a newly identified inhibitor of both innate and adaptive immunity, could improve the therapeutic efficacy of mesenchumal stromal cells （MSCs） in inflammatory bowel disease （IBD）. Methods： The expression of IL-37 in biopsied specimens of the patients with active ulcerative colitis （UC） was detected using RT-PCR and immunohistochemistry. Mice were treated with 3% dextran sulfate sodium （DSS） for 8 days to induce colitis. Before DSS treatment, the mice were injected with MSCs, MSC-eGFP or MSC-lL37b. Their body weight was measured each day, and the colons and spleens were harvested on d 10 for pathological and biochemical analyses. Results： In biopsied specimens of the patients with active UC, the expression of IL-37 was dramatically elevated in inflamed mucosa, mainly in epithelial cells and infiltrating immune cells. Compared to MSC-eGFP or MSCs, MSC-lL37b administration significantly attenuated the body weight and colon length reduction, and decreased the histological score in DSS-induced colitis mice. Furthermore, MSC-lL37b administration increased the percentage of myeloid-derived suppressor cells （MDSCs） among total splenic mononuclear cells as well as the percentage of regulatory T cells （Tregs） among splenic CD4^＋ T cells in the mice. Moreover, MSC-lL37b administration increased the IL-2^＋ cells and decreased the IFN-γ^＋ cells among splenic CD4^＋ T cells. Conclusion： IL-37 is involved in the pathophysiology of UC. IL-37b gene transfer enhances the therapeutic efficacy of MSCs in DSS- induced colitis mice by inducing Tregs and MDSCs and regulating cytokine production.Aim： To investigate whether the transfer of the IL-37b gene, a newly identified inhibitor of both innate and adaptive immunity, could improve the therapeutic efficacy of mesenchumal stromal cells （MSCs） in inflammatory bowel disease （IBD）. Methods： The expression of IL-37 in biopsied specimens of the patients with active ulcerative colitis （UC） was detected using RT-PCR and immunohistochemistry. Mice were treated with 3% dextran sulfate sodium （DSS） for 8 days to induce colitis. Before DSS treatment, the mice were injected with MSCs, MSC-eGFP or MSC-lL37b. Their body weight was measured each day, and the colons and spleens were harvested on d 10 for pathological and biochemical analyses. Results： In biopsied specimens of the patients with active UC, the expression of IL-37 was dramatically elevated in inflamed mucosa, mainly in epithelial cells and infiltrating immune cells. Compared to MSC-eGFP or MSCs, MSC-lL37b administration significantly attenuated the body weight and colon length reduction, and decreased the histological score in DSS-induced colitis mice. Furthermore, MSC-lL37b administration increased the percentage of myeloid-derived suppressor cells （MDSCs） among total splenic mononuclear cells as well as the percentage of regulatory T cells （Tregs） among splenic CD4^＋ T cells in the mice. Moreover, MSC-lL37b administration increased the IL-2^＋ cells and decreased the IFN-γ^＋ cells among splenic CD4^＋ T cells. Conclusion： IL-37 is involved in the pathophysiology of UC. IL-37b gene transfer enhances the therapeutic efficacy of MSCs in DSS- induced colitis mice by inducing Tregs and MDSCs and regulating cytokine production.

关 键 词：inflammatory bowel disease COLITIS dextran sulfate sodium-induced colitis mice mesenchymal stromal cells IL-37b regulatory T cells myeloid-derived suppressor cells inflammatory cytokines 

分 类 号：Q987[生物学—遗传学] Q254[生物学—人类学]