title: Interleukin-10 gene-carrying bifidobacteria ameliorate murine ulcerative colitis by regulating regulatory T cell/T helper 17 cell pathway.
abstract: Ulcerative colitis (UC) is a chronic inflammatory bowel disease suggested to be closely related to the imbalance of regulatory T cell/T helper 17 cell (Treg/Th17) signaling. Previously, we constructed an interleukin-10 (IL-10) expression vector, BL-hIL-10, and proved that it ameliorates dextran sulfate sodium-induced intestinal inflammation in mice. In this study, we further explored the mechanisms underlying BL-hIL-10 treatment from the Treg/Th17 imbalance perspective. Our results showed that the oral administration of BL-hIL-10 reduced the UC inflammation in mice significantly, which was assessed by disease activity index, spleen index, and pathological changes in colon tissue. Moreover, the mice after BL-hIL-10 treatment had increased proportion of Treg cells while Th17 cells decreased greatly, leading to the reconstruction of Treg/Th17 balance. Furthermore, the Th17 cell-secreted factors, such as IL-6, IL-17, and IL-23, were reduced, but the Treg-related factors, IL-10 and Transforming growth factor-β1 (TGF-β1), were elevated accordingly. Finally, Western blot confirmed the inhibition of nuclear hypoxia-inducible factor-1α (HIF-1α) and cytoplasmic mechanistic target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) in intestinal tissues. In conclusion, oral administration of BL-hIL-10 can alleviate the inflammation responses of UC in murine model through the restoration of Treg/Th17 imbalance, which might be at least partially due to the inhibition of hypoxia-mTOR-HIF-1α-Th17 axis as well as IL-6-STAT3-HIF-1α-Th17 pathway.
authors.affiliation: Department of Gastroenterology, Jinan University of Medical Sciences, Shenzhen People's Hospital, Engineering Technology Research and Development Center of Shenzhen, Shenzhen, Guangdong 518020, ChinaThe first two authors contributed to this research equally.
authors.forename: Dingguo
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Jinan University of Medical Sciences, Shenzhen People's Hospital, Engineering Technology Research and Development Center of Shenzhen, Shenzhen, Guangdong 518020, ChinaThe first two authors contributed to this research equally.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Gastroenterology, Jinan University of Medical Sciences, Shenzhen People's Hospital, Engineering Technology Research and Development Center of Shenzhen, Shenzhen, Guangdong 518020, ChinaThe first two authors contributed to this research equally.
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Gastroenterology, Jinan University of Medical Sciences, Shenzhen People's Hospital, Engineering Technology Research and Development Center of Shenzhen, Shenzhen, Guangdong 518020, ChinaThe first two authors contributed to this research equally.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Gastroenterology, Jinan University of Medical Sciences, Shenzhen People's Hospital, Engineering Technology Research and Development Center of Shenzhen, Shenzhen, Guangdong 518020, ChinaThe first two authors contributed to this research equally wangls168@163.com.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D001644:Bifidobacterium / Q000235:genetics*; D015153:Blotting, Western; D003093:Colitis, Ulcerative / Q000382:microbiology / Q000628:therapy*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D058504:Th17 Cells / Q000502:physiology*
chemical_list: D016753:Interleukin-10
keywords: T helper 17 cells; Ulcerative colitis; bifidobacteria; interleukin 10; regulatory T cells