首页 | 本学科首页   官方微博 | 高级检索  
     


IL-37b gene transfer enhances the therapeutic efficacy of mesenchumal stromal cells in DSS-induced colitis mice
Authors: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
Affiliation:1.Departments of Gastroenterology and Hepatology and Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, China;2.Departments of Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, China;3.State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China
Abstract:

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-IL37b. 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-IL37b administration significantly attenuated the body weight and colon length reduction, and decreased the histological score in DSS-induced colitis mice. Furthermore, MSC-IL37b 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-IL37b 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.
Keywords:inflammatory bowel disease   colitis   dextran sulfate sodium-induced colitis mice   mesenchymal stromal cells   IL-37b   regulatory T cells   myeloid-derived suppressor cells   inflammatory cytokines
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号