title: TSLP enhances the function of helper type 2 cells.
abstract: The cytokine thymic stromal lymphopoietin (TSLP) has been implicated in the development and progression of allergic inflammation in both humans and mice. TSLP has been shown to promote a Th2-type response through upregulation of OX40L on dendritic cells, and through direct induction of IL-4 production in naïve CD4+ T cells. However, its direct effect on effector Th cells has not been extensively investigated. In this study, we show that the level of TSLP receptor (TSLPR) expression on mouse effector Th2 cells is higher than on Th1 and Th17 cells, and that TSLP induced proliferation of effector Th2, but not Th1 nor Th17 cells. TSLP also induced the phosphorylation of signal transducer and activator of transcription (Stat) 5, and expression of the anti-apoptotic factor Bcl-2 in Th2 cells. Finally, TSLP-mediated proliferation on Th2 cells was enhanced by TCR stimulation, through IL-4-mediated induction of TSLPR expression. Taken together, these results indicate that TSLP is involved in exacerbation of mouse Th2-mediated allergic inflammation in a Th2 environment through direct stimulation of Th2 effector cells.
authors.affiliation: Immunology Program, Benaroya Research Institute, Seattle, WA 98101, USA.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kitajima
authors.forename: Hai-Chon
authors.initials: HC
authors.lastname: Lee
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D007136:Immunoglobulins; D015851:Interleukin-7; D019253:Proto-Oncogene Proteins c-bcl-2; D018121:Receptors, Cytokine; D050799:STAT5 Transcription Factor; C410591:Tslpr protein, mouse; D015847:Interleukin-4; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse