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Citations to this article

The IL-6R α chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo
Aysefa Doganci, … , Peter R. Galle, Susetta Finotto
Aysefa Doganci, … , Peter R. Galle, Susetta Finotto
Published February 1, 2005
Citation Information: J Clin Invest. 2005;115(2):313-325. https://doi.org/10.1172/JCI22433.
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Article Immunology Article has an altmetric score of 9

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

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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 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.

Authors

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

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The influence of regulatory T cells and diurnal hormone rhythms on T helper cell activity
T Bollinger, A Bollinger, J Naujoks, T Lange, W Solbach
Immunology 2010
Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function
WA Neveu, JL Allard, DM Raymond, LM Bourassa, SM Burns, JY Bunn, CG Irvin, DA Kaminsky, M Rincon
Respiratory Research 2010
Evidence for altered activity of the IL-6 pathway in chronic rhinosinusitis with nasal polyps
AT Peters, A Kato, N Zhang, DB Conley, L Suh, B Tancowny, D Carter, T Carr, M Radtke, KE Hulse, S Seshadri, R Chandra, LC Grammer, KE Harris, R Kern, RP Schleimer
Journal of Allergy and Clinical Immunology 2010
Inefficient Lymph Node Sensitization during Respiratory Viral Infection Promotes IL-17-Mediated Lung Pathology
LE Kallal, AJ Hartigan, CM Hogaboam, MA Schaller, NW Lukacs
Journal of immunology (Baltimore, Md. : 1950) 2010
Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation
G Lal, N Zhang, W der Touw, Y Ding, W Ju, EP Bottinger, SP Reid, DE Levy, JS Bromberg
Journal of immunology (Baltimore, Md. : 1950) 2009
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009
Epigenetic mechanisms of regulation of Foxp3 expression
G Lal, JS Bromberg
Blood 2009
Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters
M Feuerer, L Herrero, D Cipolletta, A Naaz, J Wong, A Nayer, J Lee, AB Goldfine, C Benoist, S Shoelson, D Mathis
Nature Medicine 2009
NOD2 Ligation Subverts IFN-α Production by Liver Plasmacytoid Dendritic Cells and Inhibits Their T Cell Allostimulatory Activity via B7-H1 Up-Regulation
A Castellaneta, TL Sumpter, L Chen, D Tokita, AW Thomson
Journal of immunology (Baltimore, Md. : 1950) 2009
IL-6 is required for airway mucus production induced by inhaled fungal allergens
WA Neveu, JB Allard, O Dienz, MJ Wargo, G Ciliberto, LA Whittaker, M Rincon
Journal of immunology (Baltimore, Md. : 1950) 2009
Rhinovirus-induced modulation of gene expression in bronchial epithelial cells from subjects with asthma
YA Bochkov, KM Hanson, S Keles, RA Brockman-Schneider, NN Jarjour, JE Gern
Mucosal Immunology 2009
Genetic ancestry modifies pharmacogenetic gene–gene interaction for asthma
Corvol H, De Giacomo A, Eng C, Seibold M, Ziv E, Chapela R, Rodriguez-Santana JR, Rodriguez-Cintron W, Thyne S, Watson HG, Meade K, LeNoir M, Avila PC, Choudhry S, Burchard EG
Pharmacogenetics and Genomics 2009
Antagonism of airway tolerance by endotoxin/lipopolysaccharide through promoting OX40L and suppressing antigen-specific Foxp3+ T regulatory cells
W Duan, T So, M Croft
Journal of immunology (Baltimore, Md. : 1950) 2008
Psychological Factors in Asthma
RJ Lieshout, G MacQueen
Allergy Asthma & Clinical Immunology 2008
Signal transducer and activator of transcription-3: a molecular hub for signaling pathways in gliomas
EC Brantley, EN Benveniste
Molecular cancer research : MCR 2008
Resolvin E1 regulates interleukin 23, interferon-gamma and lipoxin A4 to promote the resolution of allergic airway inflammation
O Haworth, M Cernadas, R Yang, CN Serhan, BD Levy
Nature Immunology 2008
New drugs targeting Th2 lymphocytes in asthma
G Caramori, D Groneberg, K Ito, P Casolari, IM Adcock, A Papi
Journal of occupational medicine and toxicology (London, England) 2008
TARC and RANTES enhance antitumor immunity induced by the GM-CSF-transduced tumor vaccine in a mouse tumor model
H Inoue, M Iga, M Xin, S Asahi, T Nakamura, R Kurita, M Nakayama, Y Nakazaki, K Takayama, Y Nakanishi, K Tani
Cancer Immunology, Immunotherapy 2008
(R)-albuterol decreases immune responses: role of activated T cells
MA Ferrada, EL Gordon, KY Jen, HZ He, X Lu, LM Barone, S Amirifeli, DL Perkins, PW Finn
Respiratory Research 2008
Interleukin-6 is crucial for recall of influenza-specific memory CD4 T cells
MP Longhi, K Wright, SN Lauder, MA Nowell, GW Jones, AJ Godkin, SA Jones, AM Gallimore
PLoS pathogens 2008
Alveolar macrophages from allergic lungs are not committed to a pro-allergic response and can reduce airway hyperresponsiveness following ex vivo culture
P Pouliot, A Spahr, É Careau, V Turmel, EY Bissonnette
Clinical & Experimental Allergy 2008
Vγ1+ γδ T cells reduce IL-10-producing CD4+CD25+ T cells in the lung of ovalbumin-sensitized and challenged mice
YS Hahn, XY Ji, SI Woo, YK Choi, MS Song, KS Shin, N Jin, RL O’Brien, WK Born
Immunology Letters 2008
Regulatory T cells and their molecular markers in peripheral blood of the patients with systemic lupus erythematosus
S Hu, W Xiao, F Kong, D Ke, R Qin, M Su
Journal of Huazhong University of Science and Technology [Medical Sciences] 2008
Prospective Study of Inhaled Corticosteroid Use, Cardiovascular Mortality, and All-Cause Mortality in Asthmatic Women
CA Camargo, RG Barr, R Chen, FE Speizer
Chest 2008
Cutting edge: soluble IL-6R is produced by IL-6R ectodomain shedding in activated CD4 T cells.
Briso EM, Dienz O, Rincon M
Journal of immunology (Baltimore, Md. : 1950) 2008
Immunosurveillance of Lung Melanoma Metastasis in EBI-3-Deficient Mice Mediated by CD8+ T Cells
Sauer KA, Maxeiner JH, Karwot R, Scholtes P, Lehr HA, Birkenbach M, Blumberg RS, Finotto S
Journal of immunology (Baltimore, Md. : 1950) 2008
Series overview: Harnessing the immune system to treat cancer
Nina Bhardwaj
Journal of Clinical Investigation 2007
Selection of probiotic bacteria for prevention of allergic diseases: immunomodulation of neonatal dendritic cells
LE Niers, MO Hoekstra, HM Timmerman, NO van Uden, PM de Graaf, HH Smits, JL Kimpen, GT Rijkers
Clinical & Experimental Immunology 2007
Classic interleukin-6 receptor signaling and interleukin-6 trans-signaling differentially control angiotensin II-dependent hypertension, cardiac signal transducer and activator of transcription-3 activation, and vascular hypertrophy in vivo
B Coles, CA Fielding, S Rose-John, J Scheller, SA Jones, VB O'Donnell
The American Journal of Pathology 2007
Nonredundant roles for Stat5a/b in directly regulating Foxp3
Z Yao, Y Kanno, M Kerenyi, G Stephens, L Durant, WT Watford, A Laurence, GW Robinson, EM Shevach, R Moriggl, L Hennighausen, C Wu, JJ O'Shea
Blood 2007
Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation
T Korn, J Reddy, W Gao, E Bettelli, A Awasthi, TR Petersen, BT Bäckström, RA Sobel, KW Wucherpfennig, TB Strom, M Oukka, VK Kuchroo
Nature Medicine 2007
Unique Gene Expression Profiles in Infants Vaccinated with Different Strains of Mycobacterium bovis Bacille Calmette-Guérin
B Wu, C Huang, L Garcia, AP de Leon, JS Osornio, M Bobadilla-del-Valle, L Ferreira, S Canizales, P Small, M Kato-Maeda, AM Krensky, C Clayberger
Infection and immunity 2007
Concentration of soluble interleukin-6 receptors in tears of allergic conjunctival disease patients.
Shoji J, Kawaguchi A, Gotoh A, Inada N, Sawa M
Japanese Journal of Ophthalmology 2007
Interleukin-10-Secreting regulatory T cells in allergy and asthma
Z Urry, E Xystrakis, CM Hawrylowicz
Current Allergy and Asthma Reports 2006
Interleukin-6 and its receptor: from bench to bedside
J Scheller, S Rose-John
Medical Microbiology and Immunology 2006
The role of immune tolerance in asthma pathogenesis
KG Tournoy, S Provoost, CV Hove, G Joos
Current Allergy and Asthma Reports 2006
Distinct roles for IL-6 and IL-12p40 in mediating protection againstLeishmania donovani and the expansion of IL-10+ CD4+ T cells
S Stäger, A Maroof, S Zubairi, SL Sanos, M Kopf, PM Kaye
European Journal of Immunology 2006
Dysfunctional T regulatory cells in multiple myeloma
RH Prabhala, P Neri, JE Bae, P Tassone, MA Shammas, CK Allam, JF Daley, D Chauhan, E Blanchard, HS Thatte, KC Anderson, NC Munshi
Blood 2006
Antibody array-generated cytokine profiles of tears of patients with vernal keratoconjunctivitis or giant papillary conjunctivitis.
Shoji J, Inada N, Sawa M
Japanese Journal of Ophthalmology 2006
The role of the FOXP3 transcription factor in the immune regulation of allergic asthma
CB Schmidt-Weber, K Blaser
Current Allergy and Asthma Reports 2005
Regulatory T cells and IL-10 in allergic inflammation: Figure. 1
CM Hawrylowicz
Journal of Experimental Medicine 2005
Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4 + CD25 + regulatory T cells is interleukin 10 dependent
J Kearley, JE Barker, DS Robinson, CM Lloyd
Journal of Experimental Medicine 2005
Pathological role of IL-6 in the experimental allergic bronchial asthma in mice.
Doganci A, Sauer K, Karwot R, Finotto S
Clinical Reviews in Allergy & Immunology 2005

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