title: DC-derived TSLP promotes Th2 polarization in LPS-primed allergic airway inflammation.
abstract: Thymic stromal lymphopoietin (TSLP) plays important roles in the pathogenesis of allergic diseases. Whether and how TSLP is involved in the initial priming of T helper type-2 (Th2) differentiation against harmless antigen remains unclear. Using an intranasal sensitization protocol with OVA and LPS, we showed that TSLP signaling is required for low-dose LPS-induced Th2 inflammation, but not for high-dose LPS-induced Th1 immunity. We further demonstrated that low-dose LPS-activated bone marrow-derived dendritic cells expressed relatively high Tslp but low Il12a, and were able to prime naïve DO11.10 T cells to differentiate into Th2 cells in a TSLP-dependent manner. After transfer into wild-type recipient mice, the low-dose LPS-activated OVA-loaded dendritic cells (DCs) induced airway eosinophilia, but primed neutrophil-dominated airway inflammation when TSLP-deficient DCs were used. These studies demonstrate that TSLP released by DCs in response to a low concentration of LPS plays a role in priming Th2 differentiation and thus may serve as a polarizing third signal, in addition to antigen/MHC class II and co-stimulatory factors, from antigen-presenting DCs to direct effector T-cell differentiation.
authors.affiliation: Institute of Biotechnology, Zhejiang University, Hangzhou, China.
authors.forename: Yanlu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xueping
authors.initials: X
authors.lastname: Zhou
authors.forename: Baohua
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004802:Eosinophilia / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D018418:Th2 Cells / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D010047:Ovalbumin; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse