title: TGF-β signaling in T cells is not essential for Th17 cell development in the mouse.
abstract: Th17 cells are potent pro-inflammatory effectors crucial for defense against extracellular bacteria. However, in this context and in the context of autoimmune disorders Th17 cells have been demonstrated to be key contributors to destructive pathological mechanism. A number of trials report TGF-beta to be involved in Th17 cell development. Nevertheless, to date, the role that TGF-beta plays in Th17 cell generation remains unclear. In this paper we highlight the role of TGF-beta in Th17 cell development in the mouse. The effects of likewise T cell specific over-expression of TGF-beta or inhibition of TGF-beta signal transduction in these cells on Th17 cell development were investigated by means of transgenic mouse models. The T cell specific insensitivity to TGF-beta does not prevent Th17 cell development ex vivo or in vitro in the murine system. In contrast, stimulation of T cells over-expressing TGF-beta actually results in decreased Th17 cell numbers in comparison to the wild type. Thus, our data indicate that TGF-beta signaling in T cells is dispensable or even inhibitory for generation of Th17 cells in the mouse. Moreover, we could show TGF-beta to inhibit a LPS driven Th1 cell development suggesting the cytokine to act as an indirect effector in Th17 cell differentiation.
authors.affiliation: Institute of Physiological Chemistry, University of Leipzig, Leipzig, Germany. julia.schumann@vmf.uni-leipzig.de
authors.forename: J
authors.initials: J
authors.lastname: Schumann
authors.forename: U
authors.initials: U
authors.lastname: Muller
authors.forename: M
authors.initials: M
authors.lastname: Blessing
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta