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  4. The IL-6R alpha chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo
 
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2005
Zeitschriftenaufsatz
Titel

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

Abstract
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.
Author(s)
Doganci, A.
Eigenbrod, T.
Krug, N.
Sanctis, G.T. de
Hausding, M.
Erpenbeck, V.J.
Haddad, E.-B.
Schmitt, E.
Bopp, T.
Kallen, K.-J.
Herz, U.
Schmitt, S.
Luft, C.
Hecht, O.
Hohlfeld, J.M.
Ito, H.
Nishimoto, N.
Yoshizaki, K.
Kishimoto, T.
Rose-John, S.
Renz, H.
Neurath, M.F.
Galle, P.R.
Finotto, S.
Zeitschrift
Journal of clinical investigation
Thumbnail Image
DOI
10.1172/JCI200522433
Language
Englisch
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Tags
  • forkhead transcriptio...

  • homeodomain protein

  • ovalbumin

  • receptor, cytokine

  • Th2 cell

  • trans-activator

  • Asthma

  • DNA binding proteins

  • Hypersensitivity

  • Inflammation

  • Lungs

  • Mice

  • Signal transduction

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