Pathologic Fibroblasts in Idiopathic Subglottic Stenosis Amplify Local Inflammatory Signals

Otolaryngol Head Neck Surg. 2019 Jan;160(1):107-115. doi: 10.1177/0194599818803584. Epub 2018 Oct 16.


Objective: To characterize the phenotype and function of fibroblasts derived from airway scar in idiopathic subglottic stenosis (iSGS) and to explore scar fibroblast response to interleukin 17A (IL-17A).

Study design: Basic science.

Setting: Laboratory.

Subjects and methods: Primary fibroblast cell lines from iSGS subjects, idiopathic pulmonary fibrosis subjects, and normal control airways were utilized for analysis. Protein, molecular, and flow cytometric techniques were applied in vitro to assess the phenotype and functional response of disease fibroblasts to IL-17A.

Results: Mechanistically, IL-17A drives iSGS scar fibroblast proliferation ( P < .01), synergizes with transforming growth factor ß1 to promote extracellular matrix production (collagen and fibronectin; P = .04), and directly stimulates scar fibroblasts to produce chemokines (chemokine ligand 2) and cytokines (IL-6 and granulocyte-macrophage colony-stimulating factor) critical to the recruitment and differentiation of myeloid cells ( P < .01). Glucocorticoids abrogated IL-17A-dependent iSGS scar fibroblast production of granulocyte-macrophage colony-stimulating factor ( P = .02).

Conclusion: IL-17A directly drives iSGS scar fibroblast proliferation, synergizes with transforming growth factor ß1 to promote extracellular matrix production, and amplifies local inflammatory signaling. Glucocorticoids appear to partially abrogate fibroblast-dependent inflammatory signaling. These results offer mechanistic support for future translational study of clinical reagents for manipulation of the IL-17A pathway in iSGS patients.

Keywords: IL-17; IL-17A; fibroblast; iSGS; idiopathic subglottis stenosis; laryngotracheal stenosis; tracheal stenosis.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy, Needle
  • Case-Control Studies
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Cicatrix / pathology*
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Fibroblasts / pathology*
  • Fibrosis / genetics
  • Fibrosis / pathology*
  • Flow Cytometry / methods
  • Humans
  • Immunohistochemistry
  • Interleukin-17 / genetics*
  • Laryngostenosis / genetics
  • Laryngostenosis / pathology*
  • Male
  • Polymerase Chain Reaction / methods
  • Reference Values
  • Sensitivity and Specificity
  • Signal Transduction / genetics


  • Cytokines
  • IL17A protein, human
  • Interleukin-17