Activation of TGF-�-induced non-Smad signaling pathways during TH17 differentiation

Abstract

Event Abstract Back to Event Activation of TGF-β-induced non-Smad signaling pathways during TH17 differentiation Steffen Haupeltshofer1*, Maruf Hasan2, Bernhard Neumann2, Klemens Angstwurm2, Ralf Gold1 and Ingo Kleiter1 1 St. Josef-Hospital, Ruhr-University Bochum, Department of Neurology, Germany 2 University of Regensburg, Department of Neurology, Germany T helper (TH)17 cells, a proinflammatory subset of effector T cells, are involved in the pathogenesis of autoimmune diseases such as multiple sclerosis. Although the cytokine TGF-β has been shown to positively regulate the development of murine interleukin (IL)-17 producing CD4+ T cells, the canonical Smad-dependent intracellular signaling pathway seems to be dispensable for TH17 differentiation. By using a protein antibody array we characterized the phosphorylation status of signaling proteins downstream of the TGF-β receptor during TH17 differentiation of naïve murine CD4+CD62L+ T cells to the TH17 phenotyp. To identify Smad-independent signaling pathways we compared the protein phosphorylation between wild type T cells and T cells with overexpression of the Smad pathway inhibitor Smad7. We found that proteins of the PI3K/AKT/mTOR pathway are activated at specific phosphorylation sites during TH17 differentiation, independently of Smad signaling. Pharmacological inhibition of these pathways caused decreased IL-17 production by differentiated TH17 cells in vitro. Our data show that Smad-independent intracellular signaling pathways contribute to TGF-β-induced TH17 differentiation, and expand our understanding of inflammatory pathways relevant for multiple sclerosis. Keywords: Th17, Smad7 Protein, differentiation, signalling, AKT/mTOR signaling Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune receptors and signaling Citation: Haupeltshofer S, Hasan M, Neumann B, Angstwurm K, Gold R and Kleiter I (2013). Activation of TGF-β-induced non-Smad signaling pathways during TH17 differentiation. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01135 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Jul 2013; Published Online: 22 Aug 2013. * Correspondence: Mr. Steffen Haupeltshofer, St. Josef-Hospital, Ruhr-University Bochum, Department of Neurology, Bochum, Germany, Steffen.Haupeltshofer@rub.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Steffen Haupeltshofer Maruf Hasan Bernhard Neumann Klemens Angstwurm Ralf Gold Ingo Kleiter Google Steffen Haupeltshofer Maruf Hasan Bernhard Neumann Klemens Angstwurm Ralf Gold Ingo Kleiter Google Scholar Steffen Haupeltshofer Maruf Hasan Bernhard Neumann Klemens Angstwurm Ralf Gold Ingo Kleiter PubMed Steffen Haupeltshofer Maruf Hasan Bernhard Neumann Klemens Angstwurm Ralf Gold Ingo Kleiter Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.