title: Induction of IL-4 expression in CD4(+) T cells by thymic stromal lymphopoietin.
abstract: The cytokine thymic stromal lymphopoietin (TSLP) has been implicated in the development and progression of allergic inflammation in both humans and mice. Although the underlying mechanism is not known, TSLP-stimulated dendritic cells have been shown to prime human CD4(+) T cells into Th2 cytokine-producing cells. However, its direct effect on CD4(+) T cells has not been extensively investigated. In this study, we show that TSLP can drive Th2 differentiation in the absence of exogenous IL-4 and APCs. IL-4 blockade inhibited TSLP-mediated Th2 differentiation, demonstrating that IL-4 is involved in this process. Further analysis has shown that TSLP-induced Th2 differentiation is dependent on Stat6 and independent of IL-2 and that TSLP treatment leads to immediate, direct Il-4 gene transcription. Taken together, these data demonstrate that TSLP is directly involved in Th2-mediated responses via the induction of IL-4 production.
authors.affiliation: Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Omori
authors.forename: Steven
authors.initials: S
authors.lastname: Ziegler
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002454:Cell Differentiation; D016207:Cytokines / Q000502:physiology*; D005786:Gene Expression Regulation; D015847:Interleukin-4 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D050800:STAT6 Transcription Factor; D017154:Stromal Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology; D014158:Transcription, Genetic; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse