title: Bone marrow-derived mesenchymal stem cells favor the immunosuppressive T cells skewing in a Helicobacter pylori model of gastric cancer.
abstract: Bone marrow-derived mesenchymal stem cells (BM-MSCs) play an important role in Helicobacter pylori-induced gastric carcinogenesis. While the mechanism is not well understood, BM-MSCs have been shown to contribute to the immunosuppressive response found in a number of diseases. Here, BM-MSCs were transplanted into the stomach of mice with a 44-week mouse-adapted H. pylori infection. At day 28 post-transplantation, BM-MSCs migrated from the subserosal to the mucosal layer of the stomach. The grafted BM-MSCs significantly stimulated systemic and local interleukin-10 (IL-10)-secreting T cell and regulatory T cell (Treg) functions. This observation was correlated with an increased percentage of CD4⁺IL-10⁺ cells and CD4⁺CD25⁺FoxP3⁺ cells in splenic mononuclear cells compared with H. pylori-infected mice not receiving BM-MSCs. Moreover, inhibitory cytokines IL-10 and transforming growth factor-β1 increased in the gastric tissue, while there was a decrease in inflammatory interferon-γ (IFN-γ). BM-MSC-transplanted mice also developed elevated IL-10/IFN-γ secreting and Treg/Th17 ratios. A coculture system in the presence or absence of BM-MSCs was also established to evaluate the immune responses in vitro. An increase in IL-10-secreting T cells and Tregs, associated with increased expression of Gata-3 and FoxP3, generation of IL-10 in the supernatant, and proliferation of gastric epithelial cells (GECs) was observed. These findings demonstrate that transplantation of BM-MSCs into a chronic H. pylori-infected mouse model results in the generation of an immunosuppressive environment. The local and systemic immunosuppression mediated by BM-MSCs likely contributed to an environment that is compatible with the development of H. pylori-induced gastric cancer.
authors.affiliation: Division of Gastroenterology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China .
authors.forename: Rong
authors.initials: R
authors.lastname: Lin
authors.forename: Huan
authors.initials: H
authors.lastname: Ma
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ding
authors.forename: Weina
authors.initials: W
authors.lastname: Shi
authors.forename: Wei
authors.initials: W
authors.lastname: Qian
authors.forename: Jun
authors.initials: J
authors.lastname: Song
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Hou
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology; D016480:Helicobacter pylori / Q000276:immunology / Q000502:physiology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000276:immunology* / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D016753:Interleukin-10; D007371:Interferon-gamma