PMID- 27296163
OWN - NLM
STAT- MEDLINE
DCOM- 20170727
LR  - 20220410
IS  - 1531-4995 (Electronic)
IS  - 0023-852X (Print)
IS  - 0023-852X (Linking)
VI  - 126
IP  - 11
DP  - 2016 Nov
TI  - Idiopathic subglottic stenosis is associated with activation of the inflammatory 
      IL-17A/IL-23 axis.
PG  - E356-E361
LID - 10.1002/lary.26098 [doi]
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 gammadelta 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.
CI  - (c) 2016 The American Laryngological, Rhinological and Otological Society, Inc.
FAU - Gelbard, Alexander
AU  - Gelbard A
AD  - Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee. 
      alexander.gelbard@vanderbilt.edu.
FAU - Katsantonis, Nicolas-George
AU  - Katsantonis NG
AD  - Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee.
FAU - Mizuta, Masanobu
AU  - Mizuta M
AD  - Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee.
FAU - Newcomb, Dawn
AU  - Newcomb D
AD  - Department of Medicine, Division of Pulmonary and Critical Care, Vanderbilt 
      University, Nashville, Tennessee.
FAU - Rotsinger, Joseph
AU  - Rotsinger J
AD  - Department of Medicine, Division of Infectious Disease, Vanderbilt University, 
      Nashville, Tennessee.
FAU - Rousseau, Bernard
AU  - Rousseau B
AD  - Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee.
FAU - Daniero, James J
AU  - Daniero JJ
AD  - Department of Otolaryngology, University of Virginia Health System, 
      Charlottesville, Virginia.
FAU - Edell, Eric S
AU  - Edell ES
AD  - Department of Medicine, Division of Pulmonary & Critical Care, Mayo Clinic, 
      Rochester, Minnesota.
FAU - Ekbom, Dale C
AU  - Ekbom DC
AD  - Department of Otolaryngology, Mayo Clinic, Rochester, Minnesota.
FAU - Kasperbauer, Jan L
AU  - Kasperbauer JL
AD  - Department of Otolaryngology, Mayo Clinic, Rochester, Minnesota.
FAU - Hillel, Alexander T
AU  - Hillel AT
AD  - Department of Otolaryngology, Johns Hopkins, Baltimore, Maryland.
FAU - Yang, Liying
AU  - Yang L
AD  - Department of Medicine, New York University School of Medicine, New York, New 
      York, U.S.A.
FAU - Garrett, C Gaelyn
AU  - Garrett CG
AD  - Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee.
FAU - Netterville, James L
AU  - Netterville JL
AD  - Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee.
FAU - Wootten, Christopher T
AU  - Wootten CT
AD  - Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee.
FAU - Francis, David O
AU  - Francis DO
AD  - Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee.
FAU - Stratton, Charles
AU  - Stratton C
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University, 
      Nashville, Tennessee.
FAU - Jenkins, Kevin
AU  - Jenkins K
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University, 
      Nashville, Tennessee.
FAU - McGregor, Tracy L
AU  - McGregor TL
AD  - Department of Pediatrics, Division of Medical Genetics, Vanderbilt University, 
      Nashville, Tennessee.
FAU - Gaddy, Jennifer A
AU  - Gaddy JA
AD  - Department of Medicine, Division of Infectious Disease, Vanderbilt University, 
      Nashville, Tennessee.
AD  - Veterans Affairs Tennessee Valley Healthcare Services, Nashville, Tennessee.
FAU - Blackwell, Timothy S
AU  - Blackwell TS
AD  - Department of Medicine, Division of Pulmonary and Critical Care, Vanderbilt 
      University, Nashville, Tennessee.
AD  - Veterans Affairs Tennessee Valley Healthcare Services, Nashville, Tennessee.
FAU - Drake, Wonder P
AU  - Drake WP
AD  - Department of Medicine, Division of Infectious Disease, Vanderbilt University, 
      Nashville, Tennessee.
LA  - eng
GR  - K23 DC013559/DC/NIDCD NIH HHS/United States
GR  - K23 DC014082/DC/NIDCD NIH HHS/United States
GR  - K24 HL127301/HL/NHLBI NIH HHS/United States
GR  - P30 CA068485/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160614
PL  - United States
TA  - Laryngoscope
JT  - The Laryngoscope
JID - 8607378
RN  - 0 (IL17A protein, human)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukin-23)
RN  - Idiopathic subglottic tracheal stenosis
SB  - IM
MH  - Airway Obstruction/etiology
MH  - Case-Control Studies
MH  - Humans
MH  - Inflammation Mediators/*physiology
MH  - Interleukin-17/*physiology
MH  - Interleukin-23/*physiology
MH  - Larynx/metabolism/pathology
MH  - Signal Transduction/*physiology
MH  - Trachea/metabolism/pathology
MH  - Tracheal Stenosis/complications/*metabolism/pathology
PMC - PMC5077677
MID - NIHMS789159
OTO - NOTNLM
OT  - IL-17
OT  - IL-17A
OT  - ISS
OT  - iSGS
OT  - idiopathic subglottis stenosis
OT  - laryngotracheal stenosis
OT  - tracheal stenosis
EDAT- 2016/10/25 06:00
MHDA- 2017/07/28 06:00
PMCR- 2017/11/01
CRDT- 2016/06/15 06:00
PHST- 2016/01/18 00:00 [received]
PHST- 2016/04/18 00:00 [revised]
PHST- 2016/04/26 00:00 [accepted]
PHST- 2016/10/25 06:00 [pubmed]
PHST- 2017/07/28 06:00 [medline]
PHST- 2016/06/15 06:00 [entrez]
PHST- 2017/11/01 00:00 [pmc-release]
AID - 10.1002/lary.26098 [doi]
PST - ppublish
SO  - Laryngoscope. 2016 Nov;126(11):E356-E361. doi: 10.1002/lary.26098. Epub 2016 Jun 
      14.