title: IL-37b gene transfer enhances the therapeutic efficacy of mesenchumal stromal cells in DSS-induced colitis mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of Gastroenterology and Hepatology and Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Wei-qiang
authors.initials: WQ
authors.lastname: Wang
authors.affiliation: Departments of Gastroenterology and Hepatology and Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Dong
authors.affiliation: Departments of Gastroenterology and Hepatology and Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Departments of Gastroenterology and Hepatology and Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Guo-hui
authors.initials: GH
authors.lastname: Jiao
authors.affiliation: Departments of Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Cong-zhong
authors.initials: CZ
authors.lastname: Zhu
authors.affiliation: Departments of Gastroenterology and Hepatology and Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Wen-wen
authors.initials: WW
authors.lastname: Li
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Wan-tong
authors.initials: WT
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Song
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Zhi-na
authors.initials: ZN
authors.lastname: Sun
authors.affiliation: Departments of Gastroenterology and Hepatology and Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Yu-ming
authors.initials: YM
authors.lastname: Wang
authors.affiliation: Departments of Gastroenterology and Hepatology and Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Wen-tian
authors.initials: WT
authors.lastname: Liu
authors.affiliation: Departments of Gastroenterology and Hepatology and Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Departments of Gastroenterology and Hepatology and Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Bang-mao
authors.initials: BM
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Xiao-ming
authors.initials: XM
authors.lastname: Feng
mesh_terms: D000818:Animals; D016207:Cytokines / Q000032:analysis; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D007375:Interleukin-1 / Q000235:genetics*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D016207:Cytokines; C508587:IL37 protein, human; D007375:Interleukin-1; D016264:Dextran Sulfate