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rdf:type |
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lifeskim:mentions |
umls-concept:C0004096,
umls-concept:C0024109,
umls-concept:C0026336,
umls-concept:C0037083,
umls-concept:C0039198,
umls-concept:C0205263,
umls-concept:C0205276,
umls-concept:C0332206,
umls-concept:C0591833,
umls-concept:C1149209,
umls-concept:C1332714,
umls-concept:C1710082,
umls-concept:C2610891
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pubmed:issue |
6
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pubmed:dateCreated |
2007-6-18
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pubmed:abstractText |
We previously reported high levels of the soluble form of the IL-6R (sIL-6R) in the airways of asthmatic subjects. Here, we analyzed the IL-6R effects on Th2 cell survival in the lung by locally antagonizing sIL-6R-mediated trans-signaling with a designer fusion protein (gp130-Fc) as well as IL-6R signaling with an antibody against the gp80 unit of the IL-6R (alphaIL-6R) in a murine model of asthma after ovalbumin peptide (OVA) sensitization and challenge. Blockade of the sIL-6R led to a significant decrease in inflammatory cells by an apoptosis-independent mechanism. In contrast, local treatment with alphaIL-6R antibodies that also block signaling via the membrane-bound IL-6R (mIL-6R) led to decreased signal transducers and activators of transcription (STAT)-3 but not STAT-1 phosphorylation in the lung of treated mice as compared with control-treated mice. Moreover, this treatment induced apoptosis of the cells present in the airways of OVA-treated mice as well as apoptosis of lung CD4+ effector T cells. Subsequent studies showed that this effect was mediated by lung CD4+CD25+Foxp3+ T regulatory cells by a cell-cell interaction, thereby contributing to the resolution of airway hyperresponsiveness in OVA-treated mice given anti-IL-6R antibodies. Taken together, these data suggest that blockade of mIL-6R signaling leads to cell death of lung effector T cells by activating regulatory T cells in experimental asthma. Local targeting of IL-6R signaling could be a novel approach for inducing Th2 T cell death in allergic airways via regulatory T cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokine Receptor gp130,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Foxp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Il6st protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fc Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Ovalbumin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Stat3 protein, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0953-8178
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pubmed:author |
pubmed-author:BorossIldikoI,
pubmed-author:DoganciAysefaA,
pubmed-author:EigenbrodTatjanaT,
pubmed-author:FinottoSusettaS,
pubmed-author:GallePeter RPR,
pubmed-author:ItoHiroakiH,
pubmed-author:KarwotRomanR,
pubmed-author:KishimotoTadamitsuT,
pubmed-author:NeurathMarkus FMF,
pubmed-author:NishimotoNorihiroN,
pubmed-author:Rose-JohnStefanS,
pubmed-author:YoshizakiKazuyukiK
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pubmed:issnType |
Print
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
685-93
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pubmed:meshHeading |
pubmed-meshheading:17496315-Animals,
pubmed-meshheading:17496315-Antibodies,
pubmed-meshheading:17496315-Apoptosis,
pubmed-meshheading:17496315-Asthma,
pubmed-meshheading:17496315-Bronchoalveolar Lavage Fluid,
pubmed-meshheading:17496315-CD4-Positive T-Lymphocytes,
pubmed-meshheading:17496315-Coculture Techniques,
pubmed-meshheading:17496315-Cytokine Receptor gp130,
pubmed-meshheading:17496315-Disease Models, Animal,
pubmed-meshheading:17496315-Female,
pubmed-meshheading:17496315-Forkhead Transcription Factors,
pubmed-meshheading:17496315-Gene Expression,
pubmed-meshheading:17496315-Immunization,
pubmed-meshheading:17496315-Immunoglobulin Fc Fragments,
pubmed-meshheading:17496315-Interleukin-6,
pubmed-meshheading:17496315-Lung,
pubmed-meshheading:17496315-Mice,
pubmed-meshheading:17496315-Mice, Inbred BALB C,
pubmed-meshheading:17496315-Ovalbumin,
pubmed-meshheading:17496315-Phosphorylation,
pubmed-meshheading:17496315-Receptors, Interleukin-6,
pubmed-meshheading:17496315-Recombinant Fusion Proteins,
pubmed-meshheading:17496315-STAT3 Transcription Factor,
pubmed-meshheading:17496315-Signal Transduction,
pubmed-meshheading:17496315-T-Lymphocytes, Regulatory
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pubmed:year |
2007
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pubmed:articleTitle |
Local blockade of IL-6R signaling induces lung CD4+ T cell apoptosis in a murine model of asthma via regulatory T cells.
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pubmed:affiliation |
Laboratory of Cellular and Molecular Immunology of the Lung, First Medical Clinic, University of Mainz, Germany. finotto@mail.uni-mainz.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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