Idiopathic subglottic stenosis is associated with activation of the inflammatory IL‐17A/IL‐23 axis
Identifieur interne : 000E10 ( Main/Exploration ); précédent : 000E09; suivant : 000E11Idiopathic subglottic stenosis is associated with activation of the inflammatory IL‐17A/IL‐23 axis
Auteurs : Alexander Gelbard [États-Unis] ; Nicolas-George Katsantonis ; Masanobu Mizuta ; Dawn Newcomb ; Joseph Rotsinger ; Bernard Rousseau ; James J. Daniero ; Eric S. Edell ; Dale C. Ekbom ; Jan L. Kasperbauer ; Alexander T. Hillel [États-Unis] ; Liying Yang [États-Unis] ; C. Gaelyn Garrett ; James L. Netterville ; Christopher T. Wootten ; David O. Francis ; Charles Stratton ; Kevin Jenkins ; Tracy L. Mcgregor ; Jennifer A. Gaddy [États-Unis] ; Timothy S. Blackwell [États-Unis] ; Wonder P. DrakeSource :
- The Laryngoscope [ 0023-852X ] ; 2016-11.
Abstract
Objectives/Hypothesis: Idiopathic subglottic stenosis (iSGS) is a rare and devastating extrathoracic obstruction involving the lower laryngeal and upper tracheal airway. It arises without known antecedent injury or associated disease process. Persistent mucosal inflammation and a localized fibrotic response are hallmarks of the disease. Despite the initial clinical description of iSGS more than 40 year ago, there have been no substantive investigations into the pathogenesis of this enigmatic and progressive airway obstruction. In these studies, we present the initial characterization of the molecular pathogenesis underlying the fibrosing phenotype of iSGS. Methods: Utilizing 20 human iSGS and healthy control specimens, we applied histologic, immunohistochemical, molecular, and immunologic techniques. Results: We demonstrate significant activation of the canonical IL‐23/IL‐17A pathway in the tracheal mucosa of iSGS patients, as well as identify γδ T cells as the primary cellular source of IL‐17A. Conclusion: Our results suggest that aberrant mucosal immune activation is a component in of the pathogenesis of iSGS. Most critically, our work offers new targets for future therapeutic intervention. Level of Evidence: NA Laryngoscope, 126:E356–E361, 2016
Url:
DOI: 10.1002/lary.26098
Affiliations:
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Daniero</name><affiliation><wicri:noCountry code="subField">Charlottesville</wicri:noCountry></affiliation></author><author><name sortKey="Edell, Eric S" sort="Edell, Eric S" uniqKey="Edell E" first="Eric S." last="Edell">Eric S. Edell</name><affiliation><wicri:noCountry code="subField">Rochester</wicri:noCountry></affiliation></author><author><name sortKey="Ekbom, Dale C" sort="Ekbom, Dale C" uniqKey="Ekbom D" first="Dale C." last="Ekbom">Dale C. Ekbom</name><affiliation><wicri:noCountry code="subField">Rochester</wicri:noCountry></affiliation></author><author><name sortKey="Kasperbauer, Jan L" sort="Kasperbauer, Jan L" uniqKey="Kasperbauer J" first="Jan L." last="Kasperbauer">Jan L. Kasperbauer</name><affiliation><wicri:noCountry code="subField">Rochester</wicri:noCountry></affiliation></author><author><name sortKey="Hillel, Alexander T" sort="Hillel, Alexander T" uniqKey="Hillel A" first="Alexander T." last="Hillel">Alexander T. Hillel</name><affiliation wicri:level="3"><country>États-Unis</country><placeName><settlement type="city">Baltimore</settlement><region type="state">Maryland</region></placeName><wicri:orgArea>Department of Otolaryngology, Johns Hopkins, Maryland</wicri:orgArea></affiliation></author><author><name sortKey="Yang, Liying" sort="Yang, Liying" uniqKey="Yang L" first="Liying" last="Yang">Liying Yang</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, New York University School of Medicine, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Garrett, C Gaelyn" sort="Garrett, C Gaelyn" uniqKey="Garrett C" first="C. Gaelyn" last="Garrett">C. Gaelyn Garrett</name><affiliation><wicri:noCountry code="subField">Nashville</wicri:noCountry></affiliation></author><author><name sortKey="Netterville, James L" sort="Netterville, James L" uniqKey="Netterville J" first="James L." last="Netterville">James L. Netterville</name><affiliation><wicri:noCountry code="subField">Nashville</wicri:noCountry></affiliation></author><author><name sortKey="Wootten, Christopher T" sort="Wootten, Christopher T" uniqKey="Wootten C" first="Christopher T." last="Wootten">Christopher T. Wootten</name><affiliation><wicri:noCountry code="subField">Nashville</wicri:noCountry></affiliation></author><author><name sortKey="Francis, David O" sort="Francis, David O" uniqKey="Francis D" first="David O." last="Francis">David O. Francis</name><affiliation><wicri:noCountry code="subField">Nashville</wicri:noCountry></affiliation></author><author><name sortKey="Stratton, Charles" sort="Stratton, Charles" uniqKey="Stratton C" first="Charles" last="Stratton">Charles Stratton</name><affiliation><wicri:noCountry code="subField">Nashville</wicri:noCountry></affiliation></author><author><name sortKey="Jenkins, Kevin" sort="Jenkins, Kevin" uniqKey="Jenkins K" first="Kevin" last="Jenkins">Kevin Jenkins</name><affiliation><wicri:noCountry code="subField">Nashville</wicri:noCountry></affiliation></author><author><name sortKey="Mcgregor, Tracy L" sort="Mcgregor, Tracy L" uniqKey="Mcgregor T" first="Tracy L." last="Mcgregor">Tracy L. Mcgregor</name><affiliation><wicri:noCountry code="subField">Nashville</wicri:noCountry></affiliation></author><author><name sortKey="Gaddy, Jennifer A" sort="Gaddy, Jennifer A" uniqKey="Gaddy J" first="Jennifer A." last="Gaddy">Jennifer A. Gaddy</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea>Department of Medicine, Division of Infectious Disease, Vanderbilt University, Nashville</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Blackwell, Timothy S" sort="Blackwell, Timothy S" uniqKey="Blackwell T" first="Timothy S." last="Blackwell">Timothy S. Blackwell</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea>Department of Medicine, Division of Pulmonary and Critical Care, Vanderbilt University, Nashville</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Drake, Wonder P" sort="Drake, Wonder P" uniqKey="Drake W" first="Wonder P." last="Drake">Wonder P. Drake</name><affiliation><wicri:noCountry code="subField">Nashville</wicri:noCountry></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">The Laryngoscope</title><title level="j" type="alt">THE LARYNGOSCOPE</title><idno type="ISSN">0023-852X</idno><idno type="eISSN">1531-4995</idno><imprint><biblScope unit="vol">126</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="E356">E356</biblScope><biblScope unit="page" to="E361">E361</biblScope><biblScope unit="page-count">6</biblScope><date type="published" when="2016-11">2016-11</date></imprint><idno type="ISSN">0023-852X</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0023-852X</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Objectives/Hypothesis: Idiopathic subglottic stenosis (iSGS) is a rare and devastating extrathoracic obstruction involving the lower laryngeal and upper tracheal airway. It arises without known antecedent injury or associated disease process. Persistent mucosal inflammation and a localized fibrotic response are hallmarks of the disease. Despite the initial clinical description of iSGS more than 40 year ago, there have been no substantive investigations into the pathogenesis of this enigmatic and progressive airway obstruction. In these studies, we present the initial characterization of the molecular pathogenesis underlying the fibrosing phenotype of iSGS. Methods: Utilizing 20 human iSGS and healthy control specimens, we applied histologic, immunohistochemical, molecular, and immunologic techniques. Results: We demonstrate significant activation of the canonical IL‐23/IL‐17A pathway in the tracheal mucosa of iSGS patients, as well as identify γδ T cells as the primary cellular source of IL‐17A. Conclusion: Our results suggest that aberrant mucosal immune activation is a component in of the pathogenesis of iSGS. Most critically, our work offers new targets for future therapeutic intervention. Level of Evidence: NA Laryngoscope, 126:E356–E361, 2016</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li><li>Tennessee</li><li>État de New York</li></region><settlement><li>Baltimore</li></settlement></list><tree><noCountry><name sortKey="Daniero, James J" sort="Daniero, James J" uniqKey="Daniero J" first="James J." last="Daniero">James J. Daniero</name><name sortKey="Drake, Wonder P" sort="Drake, Wonder P" uniqKey="Drake W" first="Wonder P." last="Drake">Wonder P. Drake</name><name sortKey="Edell, Eric S" sort="Edell, Eric S" uniqKey="Edell E" first="Eric S." last="Edell">Eric S. Edell</name><name sortKey="Ekbom, Dale C" sort="Ekbom, Dale C" uniqKey="Ekbom D" first="Dale C." last="Ekbom">Dale C. Ekbom</name><name sortKey="Francis, David O" sort="Francis, David O" uniqKey="Francis D" first="David O." last="Francis">David O. Francis</name><name sortKey="Garrett, C Gaelyn" sort="Garrett, C Gaelyn" uniqKey="Garrett C" first="C. Gaelyn" last="Garrett">C. Gaelyn Garrett</name><name sortKey="Jenkins, Kevin" sort="Jenkins, Kevin" uniqKey="Jenkins K" first="Kevin" last="Jenkins">Kevin Jenkins</name><name sortKey="Kasperbauer, Jan L" sort="Kasperbauer, Jan L" uniqKey="Kasperbauer J" first="Jan L." last="Kasperbauer">Jan L. Kasperbauer</name><name sortKey="Katsantonis, Nicolas Eorge" sort="Katsantonis, Nicolas Eorge" uniqKey="Katsantonis N" first="Nicolas-George" last="Katsantonis">Nicolas-George Katsantonis</name><name sortKey="Mcgregor, Tracy L" sort="Mcgregor, Tracy L" uniqKey="Mcgregor T" first="Tracy L." last="Mcgregor">Tracy L. Mcgregor</name><name sortKey="Mizuta, Masanobu" sort="Mizuta, Masanobu" uniqKey="Mizuta M" first="Masanobu" last="Mizuta">Masanobu Mizuta</name><name sortKey="Netterville, James L" sort="Netterville, James L" uniqKey="Netterville J" first="James L." last="Netterville">James L. Netterville</name><name sortKey="Newcomb, Dawn" sort="Newcomb, Dawn" uniqKey="Newcomb D" first="Dawn" last="Newcomb">Dawn Newcomb</name><name sortKey="Rotsinger, Joseph" sort="Rotsinger, Joseph" uniqKey="Rotsinger J" first="Joseph" last="Rotsinger">Joseph Rotsinger</name><name sortKey="Rousseau, Bernard" sort="Rousseau, Bernard" uniqKey="Rousseau B" first="Bernard" last="Rousseau">Bernard Rousseau</name><name sortKey="Stratton, Charles" sort="Stratton, Charles" uniqKey="Stratton C" first="Charles" last="Stratton">Charles Stratton</name><name sortKey="Wootten, Christopher T" sort="Wootten, Christopher T" uniqKey="Wootten C" first="Christopher T." last="Wootten">Christopher T. Wootten</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Gelbard, Alexander" sort="Gelbard, Alexander" uniqKey="Gelbard A" first="Alexander" last="Gelbard">Alexander Gelbard</name></noRegion><name sortKey="Blackwell, Timothy S" sort="Blackwell, Timothy S" uniqKey="Blackwell T" first="Timothy S." last="Blackwell">Timothy S. Blackwell</name><name sortKey="Gaddy, Jennifer A" sort="Gaddy, Jennifer A" uniqKey="Gaddy J" first="Jennifer A." last="Gaddy">Jennifer A. Gaddy</name><name sortKey="Gelbard, Alexander" sort="Gelbard, Alexander" uniqKey="Gelbard A" first="Alexander" last="Gelbard">Alexander Gelbard</name><name sortKey="Hillel, Alexander T" sort="Hillel, Alexander T" uniqKey="Hillel A" first="Alexander T." last="Hillel">Alexander T. Hillel</name><name sortKey="Yang, Liying" sort="Yang, Liying" uniqKey="Yang L" first="Liying" last="Yang">Liying Yang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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