title: Increased antigen presentation but impaired T cells priming after upregulation of interferon-beta induced by lipopolysaccharides is mediated by upregulation of B7H1 and GITRL.
abstract: Dendritic cells are able to present Ag-derived peptides on MHC class I and II molecules and induce T cells priming. Lipopolysaccharides (LPS), an activator of Toll-like 4 receptor (TLR4) signaling, has been demonstrated to facilitate Ag-presentation, up-regulate surface molecules expression but impair T cells priming. In this study, we investigated the effect of LPS on nicotine-enhanced DCs-dependent T cells priming and the mechanisms of LPS orchestrating the immunosuppressive program. We could demonstrate that the treatment with LPS resulted in increased surface molecules expression, enhanced Ag-presentation, up-regulated release of TGF-beta, TNF-alpha, IL-6, and IFN-beta. Concomititantly, the upregulation of IFN-beta in DCs induces the up-regulation of coinhibitory molecules B7H1 and GITRL, which cause an impaired activation of naïve Ag-specific T cells and the induction of T cell tolerance by enhancing B7H1-PD-1 interactions and promoting GITRL-GITL facilitated Treg generation, respectively. These data provide a mechanistic basis for the immunomodulatory action of IFN-beta which might open new possibilities in the development of therapeutic approaches aimed at the control of excessive immune response and persistent infection.
authors.affiliation: Department of Immunology, Medical College, Xiamen University, Xiamen, China; Department of Basic Medicine Science, NanYang Medical College, Nanyang, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Immunology, Medical College, Xiamen University, Xiamen, China.
authors.forename: Yan Yan
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Department of Immunology, Medical College, Xiamen University, Xiamen, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Immunology, Medical College, Xiamen University, Xiamen, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: You
authors.affiliation: Department of Immunology, Medical College, Xiamen University, Xiamen, China.
authors.forename: Xin Hui
authors.initials: XH
authors.lastname: Qiu
authors.affiliation: Department of Immunology, Medical College, Xiamen University, Xiamen, China.
authors.forename: Yi Nan
authors.initials: YN
authors.lastname: Wang
authors.affiliation: Department of Immunology, Medical College, Xiamen University, Xiamen, China.
authors.forename: Feng Guang
authors.initials: FG
authors.lastname: Gao
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects* / Q000276:immunology; D060890:B7-H1 Antigen / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects; D016899:Interferon-beta / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D048069:Tumor Necrosis Factors / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects* / Q000276:immunology
chemical_list: D060890:B7-H1 Antigen; D015850:Interleukin-6; D008070:Lipopolysaccharides; C478966:Tnfsf18 protein, mouse; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D016899:Interferon-beta