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

• Published in: The Journal of clinical investigation 2005-02, Vol.115 (2), p.313
• Main Authors: Doganci, Aysefa, Eigenbrod, Tatjana, Krug, Norbert, De Sanctis, George T
• Format: Article
• Language: English
• Subjects: Allergens; Allergies; Antigens; Asthma; Biomedical research; Cytokines; Glycoproteins; Kinases; Lavage; Lymphocytes
• ISSN: 0021-9738; 1558-8238

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.