Published May 2, 2005 - More info
The 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 α 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.
Aysefa Doganci, Tatjana Eigenbrod, Norbert Krug, George T. De Sanctis, Michael Hausding, Veit J. Erpenbeck, El-Bdaoui Haddad, Edgar Schmitt, Tobias Bopp, Karl-J. Kallen, Udo Herz, Steffen Schmitt, Cornelia Luft, Olaf Hecht, Jens M. Hohlfeld, Hiroaki Ito, Norihiro Nishimoto, Kazuyuki Yoshizaki, Tadamitsu Kishimoto, Stefan Rose-John, Harald Renz, Markus F. Neurath, Peter R. Galle, Susetta Finotto
Original citation: J. Clin. Invest.115:313–325 (2005). doi:10.1172/JCI22433
Citation for this corrigendum: J. Clin. Invest.115:1388 (2005). doi:10.1172/JCI22433C1
Aysefa Doganci,1 Tatjana Eigenbrod,1 Norbert Krug,2 George T. De Sanctis,3 Michael Hausding,1 Veit J. Erpenbeck,2 El-Bdaoui Haddad,2 Hans A. Lehr,4 Edgar Schmitt,5 Tobias Bopp,5 Karl-J. Kallen,6 Udo Herz,7 Steffen Schmitt,8 Cornelia Luft,1 Olaf Hecht,2 Jens M. Hohlfeld,2 Hiroaki Ito,9 Norihiro Nishimoto,9 Kazuyuki Yoshizaki,10 Tadamitsu Kishimoto,10 Stefan Rose-John,6 Harald Renz,7 Markus F. Neurath,11 Peter R. Galle,11 and Susetta Finotto1
1Laboratory of Cellular and Molecular Immunology of the Lung, First Medical Clinic, University of Mainz, Mainz, Germany. 2Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany. 3Respiratory Pharmacology Department, Aventis Pharmaceuticals, Bridgewater, New Jersey, USA. 4Department of Pathology and 5Institute of Immunology, University of Mainz, Mainz, Germany. 6Institute of Biochemistry, University of Kiel, Kiel, Germany. 7Department of Clinical Chemistry and Molecular Diagnostics, University of Marburg, Marburg, Germany. 8FACS Core Facility, Department of Toxicology, University of Mainz, Mainz, Germany. 9Department of Host Defence, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. 10Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. 11Laboratory of Immunology, First Medical Clinic, University of Mainz, Mainz, Germany.
H.A. Lehr’s present address is: Institute Universitaire de Pathologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
The authors regret this error.