title: Antigen-specific TGF-β-induced regulatory T cells secrete chemokines, regulate T cell trafficking, and suppress ongoing autoimmunity.
abstract: The ability to regulate ongoing inflammation using regulatory T cells (Tregs) is under intense investigation. Strategies to induce and expand Ag-specific Tregs are being developed, and whether various types of Tregs are suppressive in the inflammatory conditions associated with ongoing disease needs to be determined. In this study, we report that TGF-β-induced Tregs (iTregs) and expanded Tregs specific for a major self-Ag in autoimmune gastritis suppress inflammation and associated pathology when administered late in the process of ongoing disease. Transferred iTregs localized to the stomach, maintained Foxp3 and suppressor functions, and engaged several distinct mechanisms to alleviate disease progression. In addition to suppressing the production of inflammatory cytokines in the stomach and preventing the destruction of parietal cells, we show that iTregs secrete numerous chemokines and regulate both iTreg and effector T cell trafficking into the stomach. These data support efforts to use iTregs in therapies to treat autoimmunity and inflammatory diseases and provide novel insight into the biological mechanisms of iTreg-mediated immune suppression.
authors: Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine, St. Louis, MO 63104, USA.
authors: Thanh-Long M
authors: TL
authors: Nguyen
authors: Nicole L
authors: NL
authors: Sullivan
authors: Mark
authors: M
authors: Ebel
authors: Ryan M
authors: RM
authors: Teague
authors: Richard J
authors: RJ
authors: DiPaolo
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002465:Cell Movement / Q000276:immunology*; D018925:Chemokines / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013270:Stomach / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000378:metabolism
chemical_list: D001324:Autoantigens; D018925:Chemokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016212:Transforming Growth Factor beta