title: TLR5 signaling enhances the proliferation of human allogeneic CD40-activated B cell induced CD4hiCD25+ regulatory T cells.
abstract: Although diverse functions of different toll-like receptors (TLR) on human natural regulatory T cells have been demonstrated recently, the role of TLR-related signals on human induced regulatory T cells remain elusive. Previously our group developed an ex vivo high-efficient system in generating human alloantigen-specific CD4(hi)CD25(+) regulatory T cells from naïve CD4(+)CD25(-) T cells using allogeneic CD40-activated B cells as stimulators. In this study, we investigated the role of TLR5-related signals on the generation and function of these novel CD4(hi)CD25(+) regulatory T cells. It was found that induced CD4(hi)CD25(+) regulatory T cells expressed an up-regulated level of TLR5 compared to their precursors. The blockade of TLR5 using anti-TLR5 antibodies during the co-culture decreased CD4(hi)CD25(+) regulatory T cells proliferation by induction of S phase arrest. The S phase arrest was associated with reduced ERK1/2 phosphorylation. However, TLR5 blockade did not decrease the CTLA-4, GITR and FOXP3 expressions, and the suppressive function of CD4(hi)CD25(+) regulatory T cells. In conclusion, we discovered a novel function of TLR5-related signaling in enhancing the proliferation of CD4(hi)CD25(+) regulatory T cells by promoting S phase progress but not involved in the suppressive function of human CD40-activated B cell-induced CD4(hi)CD25(+) regulatory T cells, suggesting a novel role of TLR5-related signals in the generation of induced regulatory T cells.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong. Hong Kong SAR, China.
authors.forename: Ping-Lung
authors.initials: PL
authors.lastname: Chan
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.forename: Yinping
authors.initials: Y
authors.lastname: Liu
authors.forename: Kwok-Tai
authors.initials: KT
authors.lastname: Lam
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiang
authors.forename: Huawei
authors.initials: H
authors.lastname: Mao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Qin
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
authors.forename: Wenwei
authors.initials: W
authors.lastname: Tu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D019013:CD40 Antigens / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D059807:S Phase Cell Cycle Checkpoints; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D051198:Toll-Like Receptor 5 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D019013:CD40 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D051198:Toll-Like Receptor 5; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3