Details

Autor(en) / Beteiligte

• Doganci, Aysefa
• Eigenbrod, Tatjana
• Krug, Norbert
• De Sanctis, George T
• Hausding, Michael
• Erpenbeck, Veit J
• Haddad, El-Bdaoui
• Lehr, Hans A
• Schmitt, Edgar
• Bopp, Tobias
• Kallen, Karl-J
• Herz, Udo
• Schmitt, Steffen
• Luft, Cornelia
• Hecht, Olaf
• Hohlfeld, Jens M
• Ito, Hiroaki
• Nishimoto, Norihiro
• Yoshizaki, Kazuyuki
• Kishimoto, Tadamitsu
• Rose-John, Stefan
• Renz, Harald
• Neurath, Markus F
• Galle, Peter R
• Finotto, Susetta

Titel

The IL-6R alpha chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo

Ist Teil von

• The Journal of clinical investigation, 2005-02, Vol.115 (2), p.313-325

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2005

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 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.