title: Mycobacterium bovis Bacillus Calmette-Guérin suppresses inflammatory Th2 responses by inducing functional alteration of TSLP-activated dendritic cells.
abstract: Allergic diseases such as atopic dermatitis and asthma develop as a consequence of dysregulated T(h)2 responses. Recently, it has been demonstrated that interaction between dendritic cells (DCs) and thymic stromal lymphopoietin (TSLP), an IL-7-like cytokine, is essential for evoking T(h)2 responses in allergy. In this study, we investigated whether Mycobacterium bovis Bacillus Calmette-Guérin (BCG), a strong T(h)1 response-inducing adjuvant, can alter the function of DCs activated by TSLP (TSLP-DCs). We demonstrated that BCG redirects TSLP-DCs away from inducing inflammatory T(h)2 cells that produce IL-4, IL-5, IL-13 and tumor necrosis factor (TNF)-alpha and toward regulatory T(h)1 cells that produce IFN-gamma and IL-10. We also demonstrated that this functional alteration of TSLP-DCs by BCG depended on both production of IL-12 from DCs and down-regulation of OX40 ligand, a member of the TNF family, on DCs. These findings suggest that BCG might be a useful adjuvant for the treatment of allergic diseases that are triggered by TSLP.
authors.affiliation: First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokoi
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Amakawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tanijiri
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Yoshitaro
authors.initials: Y
authors.lastname: Torii
authors.forename: Hideki
authors.initials: H
authors.lastname: Amuro
authors.forename: Yonsu
authors.initials: Y
authors.lastname: Son
authors.forename: Kenichirou
authors.initials: K
authors.lastname: Tajima
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Tomoki
authors.initials: T
authors.lastname: Ito
authors.forename: Shirou
authors.initials: S
authors.lastname: Fukuhara
mesh_terms: D001500:BCG Vaccine / Q000276:immunology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000276:immunology; D009164:Mycobacterium Infections / Q000276:immunology* / Q000517:prevention & control; D009163:Mycobacterium bovis; D053278:OX40 Ligand / Q000037:antagonists & inhibitors; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; D053278:OX40 Ligand; D000094632:Thymic Stromal Lymphopoietin