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

  
@article{APS9276,
	author = {Wei-qiang WANG and Kui DONG and Lu ZHOU and Guo-hui JIAO and Cong-zhong ZHU and Wen-wen LI and Gang YU and Wan-tong WU and Song CHEN and Zhi-na SUN and Yu-ming WANG and Wen-tian LIU and Jie ZHANG and Bang-mao WANG and Xiao-ming FENG},
	title = {IL-37b gene transfer enhances the therapeutic efficacy of mesenchumal stromal cells in DSSinduced colitis mice},
	journal = {Acta Pharmacologica Sinica},
	volume = {36},
	number = {11},
	year = {2017},
	keywords = {},
	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 DSSinduced colitis mice by inducing Tregs and MDSCs and regulating cytokine production.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/9276}
}