Doganci, A.A.DoganciEigenbrod, T.T.EigenbrodKrug, N.N.KrugSanctis, G.T. deG.T. deSanctisHausding, M.M.HausdingErpenbeck, V.J.V.J.ErpenbeckHaddad, E.-B.E.-B.HaddadSchmitt, E.E.SchmittBopp, T.T.BoppKallen, K.-J.K.-J.KallenHerz, U.U.HerzSchmitt, S.S.SchmittLuft, C.C.LuftHecht, O.O.HechtHohlfeld, J.M.J.M.HohlfeldIto, H.H.ItoNishimoto, N.N.NishimotoYoshizaki, K.K.YoshizakiKishimoto, T.T.KishimotoRose-John, S.S.Rose-JohnRenz, H.H.RenzNeurath, M.F.M.F.NeurathGalle, P.R.P.R.GalleFinotto, S.S.Finotto2022-03-032022-03-032005https://publica.fraunhofer.de/handle/publica/20797310.1172/JCI200522433The cytokine IL-6 acts via a specific receptor complex that consists of the membrane-bound IL-6 receptor (mIL-6R) or the soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (gp130). In this study, we investigated the role of IL-6R components in asthma. We observed increased levels of sIL-6R in the airways of patients with allergic asthma as compared to those in controls. In addition, local blockade of the sIL-6R in a murine model of late-phase asthma after OVA sensitization by gp130-fraction constant led to suppression of Th2 cells in the lung. By contrast, blockade of mIL-6R induced local expansion of Foxp3-positive CD4+CD25+ Tregs with increased immunosuppressive capacities. CD4+CD25+ but not CD4+CD25- lung T cells selectively expressed the IL-6R alpha chain and showed IL-6-dependent STAT-3 phosphorylation. Finally, in an in vivo transfer model of asthma in immunodeficient Rag1 mice, CD4+CD25+ T cells isolated from anti-IL-6R antibody-treated mice exhibited marked immunosuppressive and antiinflammatory functions. IL-6 signaling therefore controls the balance between effector cells and Tregs in the lung by means of different receptor components. Furthermore, inhibition of IL-6 signaling emerges as a novel molecular approach for the treatment of allergic asthma.enforkhead transcription factorhomeodomain proteinovalbuminreceptor, cytokineTh2 celltrans-activatorAsthmaDNA binding proteinsHypersensitivityInflammationLungsMiceSignal transduction615610620journal article