Idiopathic subglottic stenosis is associated with activation of the inflammatory IL-17A/IL-23 axis

Alexander Gelbard; 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; Liying Yang; C. Gaelyn Garrett; James L. Netterville; Christopher T. Wootten; David O. Francis; Charles Stratton; Kevin Jenkins; Tracy L. McGregor; Jennifer A. Gaddy; Timothy S. Blackwell; Wonder P. Drake

doi:10.1002/lary.26098

Idiopathic subglottic stenosis is associated with activation of the inflammatory IL-17A/IL-23 axis

Alexander Gelbard, 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, Liying Yang, C. Gaelyn Garrett, James L. Netterville, Christopher T. Wootten, David O. Francis, Charles Stratton, Kevin Jenkins, Tracy L. McGregor, Jennifer A. GaddyTimothy S. Blackwell, Wonder P. Drake

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

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.

Original language	English (US)
Pages (from-to)	E356-E361
Journal	Laryngoscope
Volume	126
Issue number	11
DOIs	https://doi.org/10.1002/lary.26098
State	Published - Nov 1 2016

Keywords

IL-17
IL-17A
ISS
iSGS
idiopathic subglottis stenosis
laryngotracheal stenosis
tracheal stenosis

ASJC Scopus subject areas

Otorhinolaryngology

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10.1002/lary.26098

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Gelbard, A., Katsantonis, N. G., Mizuta, M., Newcomb, D., Rotsinger, J., Rousseau, B., Daniero, J. J., Edell, E. S., Ekbom, D. C., Kasperbauer, J. L., Hillel, A. T., Yang, L., Garrett, C. G., Netterville, J. L., Wootten, C. T., Francis, D. O., Stratton, C., Jenkins, K., McGregor, T. L., ... Drake, W. P. (2016). Idiopathic subglottic stenosis is associated with activation of the inflammatory IL-17A/IL-23 axis. Laryngoscope, 126(11), E356-E361. https://doi.org/10.1002/lary.26098

Gelbard, A, Katsantonis, NG, Mizuta, M, Newcomb, D, Rotsinger, J, Rousseau, B, Daniero, JJ, Edell, ES, Ekbom, DC, Kasperbauer, JL, Hillel, AT, Yang, L, Garrett, CG, Netterville, JL, Wootten, CT, Francis, DO, Stratton, C, Jenkins, K, McGregor, TL, Gaddy, JA, Blackwell, TS & Drake, WP 2016, 'Idiopathic subglottic stenosis is associated with activation of the inflammatory IL-17A/IL-23 axis', Laryngoscope, vol. 126, no. 11, pp. E356-E361. https://doi.org/10.1002/lary.26098

@article{4a06b947101346ad825d26d903e193cd,

title = "Idiopathic subglottic stenosis is associated with activation of the inflammatory IL-17A/IL-23 axis",

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.",

keywords = "IL-17, IL-17A, ISS, iSGS, idiopathic subglottis stenosis, laryngotracheal stenosis, tracheal stenosis",

author = "Alexander Gelbard and Katsantonis, {Nicolas George} and Masanobu Mizuta and Dawn Newcomb and Joseph Rotsinger and Bernard Rousseau and Daniero, {James J.} and Edell, {Eric S.} and Ekbom, {Dale C.} and Kasperbauer, {Jan L.} and Hillel, {Alexander T.} and Liying Yang and Garrett, {C. Gaelyn} and Netterville, {James L.} and Wootten, {Christopher T.} and Francis, {David O.} and Charles Stratton and Kevin Jenkins and McGregor, {Tracy L.} and Gaddy, {Jennifer A.} and Blackwell, {Timothy S.} and Drake, {Wonder P.}",

note = "Publisher Copyright: {\textcopyright} 2016 The American Laryngological, Rhinological and Otological Society, Inc.",

year = "2016",

month = nov,

day = "1",

doi = "10.1002/lary.26098",

language = "English (US)",

volume = "126",

pages = "E356--E361",

journal = "Laryngoscope",

issn = "0023-852X",

publisher = "John Wiley and Sons Inc.",

number = "11",

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TY - JOUR

T1 - Idiopathic subglottic stenosis is associated with activation of the inflammatory IL-17A/IL-23 axis

AU - Gelbard, Alexander

AU - Katsantonis, Nicolas George

AU - Mizuta, Masanobu

AU - Newcomb, Dawn

AU - Rotsinger, Joseph

AU - Rousseau, Bernard

AU - Daniero, James J.

AU - Edell, Eric S.

AU - Ekbom, Dale C.

AU - Kasperbauer, Jan L.

AU - Hillel, Alexander T.

AU - Yang, Liying

AU - Garrett, C. Gaelyn

AU - Netterville, James L.

AU - Wootten, Christopher T.

AU - Francis, David O.

AU - Stratton, Charles

AU - Jenkins, Kevin

AU - McGregor, Tracy L.

AU - Gaddy, Jennifer A.

AU - Blackwell, Timothy S.

AU - Drake, Wonder P.

PY - 2016/11/1

Y1 - 2016/11/1

N2 - 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.

AB - 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.

KW - IL-17

KW - IL-17A

KW - ISS

KW - iSGS

KW - idiopathic subglottis stenosis

KW - laryngotracheal stenosis

KW - tracheal stenosis

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U2 - 10.1002/lary.26098

DO - 10.1002/lary.26098

M3 - Article

C2 - 27296163

AN - SCOPUS:84977111776

SN - 0023-852X

VL - 126

SP - E356-E361

JO - Laryngoscope

JF - Laryngoscope

IS - 11

ER -

Idiopathic subglottic stenosis is associated with activation of the inflammatory IL-17A/IL-23 axis

Abstract

Keywords

ASJC Scopus subject areas

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