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

J Clin Invest. 2005 Feb;115(2):313-25. doi: 10.1172/JCI22433.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antibodies / administration & dosage
  • Antibodies / immunology
  • Asthma / immunology*
  • Asthma / pathology
  • DNA-Binding Proteins / immunology
  • Female
  • Forkhead Transcription Factors
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / immunology
  • Humans
  • Hypersensitivity / immunology*
  • Hypersensitivity / pathology
  • Inflammation / immunology
  • Inflammation / pathology
  • Lung / immunology*
  • Lung / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Ovalbumin / metabolism
  • Receptors, Cytokine / immunology
  • Receptors, Interleukin-2 / immunology*
  • Receptors, Interleukin-6 / immunology*
  • STAT3 Transcription Factor
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Th2 Cells / immunology*
  • Th2 Cells / pathology
  • Trans-Activators / immunology


  • Antibodies
  • DNA-Binding Proteins
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Homeodomain Proteins
  • Receptors, Cytokine
  • Receptors, Interleukin-2
  • Receptors, Interleukin-6
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat3 protein, mouse
  • Trans-Activators
  • cytokine receptor, GLM-R
  • RAG-1 protein
  • Ovalbumin