T-Helper 2 Lymphocyte Immunophenotype Is Associated With Iatrogenic Laryngotracheal Stenosis

Alexander Tell Hillel, Dacheng Ding, Idris Samad, Michael K. Murphy, Kevin Motz

Research output: Contribution to journalArticle

Abstract

Objective/Hypothesis: This prospective controlled human and murine study assessed the presence of inflammatory cells and cytokines to test the hypothesis that immune cells are associated with fibroproliferation in iatrogenic laryngotracheal stenosis (iLTS). Methods: Inflammation was assessed by histology and immunofluorescence (IF), quantitative real-time polymerase chain reaction (qRT-PCR), and flow cytometry of cricotracheal resections of iLTS patients compared to normal controls. An iLTS murine model assessed the temporal relationship between inflammation and fibrosis. Results: iLTS specimens showed increased inflammation versus normal controls (159/high power field [hpf] vs. 119/hpf, P = 0.038), and increased CD3 + T-cells, CD4 + cells, and CD3+/CD4 + T-helper (TH) cells (all P < 0.05). The inflammatory infiltrate was located immediately adjacent to the epithelial surface in the superficial aspect of the thickened lamina propria. Human flow cytometry and qRT-PCR showed a significant increase in interleukin (IL)-4 gene expression, indicating a TH2 phenotype. Murine IF revealed a dense CD4 + T-cell inflammatory infiltrate on day 4 to 7 postinjury, which preceded the development of fibrosis. Murine flow cytometry and qRT-PCR studies mirrored the human ones, with increased T-helper cells and IL-4 in iLTS versus normal controls. Conclusion: CD3/CD4 + T-helper lymphocytes and the proinflammatory cytokine IL-4 are associated with iLTS. The association of a TH2 immunophenotype with iLTS is consistent with findings in other fibroinflammatory disorders. The murine results reveal that the inflammatory infiltrate precedes the development of fibrosis. However, human iLTS specimens with well-developed fibrosis also contain a marked chronic inflammatory infiltrate, suggesting that the continued release of IL-4 by T-helper lymphocytes may continue to propagate iLTS. Level of Evidence: NA. Laryngoscope, 2018.

Original languageEnglish (US)
JournalLaryngoscope
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Helper-Inducer T-Lymphocytes
Pathologic Constriction
Interleukin-4
Fibrosis
Real-Time Polymerase Chain Reaction
Flow Cytometry
Inflammation
Fluorescent Antibody Technique
Cytokines
T-Lymphocytes
Laryngoscopes
Histology
Mucous Membrane
Phenotype
Gene Expression

Keywords

  • fibrosis
  • human study
  • Laryngotracheal stenosis
  • murine model
  • T-lymphocytes

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

T-Helper 2 Lymphocyte Immunophenotype Is Associated With Iatrogenic Laryngotracheal Stenosis. / Hillel, Alexander Tell; Ding, Dacheng; Samad, Idris; Murphy, Michael K.; Motz, Kevin.

In: Laryngoscope, 01.01.2018.

Research output: Contribution to journalArticle

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abstract = "Objective/Hypothesis: This prospective controlled human and murine study assessed the presence of inflammatory cells and cytokines to test the hypothesis that immune cells are associated with fibroproliferation in iatrogenic laryngotracheal stenosis (iLTS). Methods: Inflammation was assessed by histology and immunofluorescence (IF), quantitative real-time polymerase chain reaction (qRT-PCR), and flow cytometry of cricotracheal resections of iLTS patients compared to normal controls. An iLTS murine model assessed the temporal relationship between inflammation and fibrosis. Results: iLTS specimens showed increased inflammation versus normal controls (159/high power field [hpf] vs. 119/hpf, P = 0.038), and increased CD3 + T-cells, CD4 + cells, and CD3+/CD4 + T-helper (TH) cells (all P < 0.05). The inflammatory infiltrate was located immediately adjacent to the epithelial surface in the superficial aspect of the thickened lamina propria. Human flow cytometry and qRT-PCR showed a significant increase in interleukin (IL)-4 gene expression, indicating a TH2 phenotype. Murine IF revealed a dense CD4 + T-cell inflammatory infiltrate on day 4 to 7 postinjury, which preceded the development of fibrosis. Murine flow cytometry and qRT-PCR studies mirrored the human ones, with increased T-helper cells and IL-4 in iLTS versus normal controls. Conclusion: CD3/CD4 + T-helper lymphocytes and the proinflammatory cytokine IL-4 are associated with iLTS. The association of a TH2 immunophenotype with iLTS is consistent with findings in other fibroinflammatory disorders. The murine results reveal that the inflammatory infiltrate precedes the development of fibrosis. However, human iLTS specimens with well-developed fibrosis also contain a marked chronic inflammatory infiltrate, suggesting that the continued release of IL-4 by T-helper lymphocytes may continue to propagate iLTS. Level of Evidence: NA. Laryngoscope, 2018.",
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AU - Motz, Kevin

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AB - Objective/Hypothesis: This prospective controlled human and murine study assessed the presence of inflammatory cells and cytokines to test the hypothesis that immune cells are associated with fibroproliferation in iatrogenic laryngotracheal stenosis (iLTS). Methods: Inflammation was assessed by histology and immunofluorescence (IF), quantitative real-time polymerase chain reaction (qRT-PCR), and flow cytometry of cricotracheal resections of iLTS patients compared to normal controls. An iLTS murine model assessed the temporal relationship between inflammation and fibrosis. Results: iLTS specimens showed increased inflammation versus normal controls (159/high power field [hpf] vs. 119/hpf, P = 0.038), and increased CD3 + T-cells, CD4 + cells, and CD3+/CD4 + T-helper (TH) cells (all P < 0.05). The inflammatory infiltrate was located immediately adjacent to the epithelial surface in the superficial aspect of the thickened lamina propria. Human flow cytometry and qRT-PCR showed a significant increase in interleukin (IL)-4 gene expression, indicating a TH2 phenotype. Murine IF revealed a dense CD4 + T-cell inflammatory infiltrate on day 4 to 7 postinjury, which preceded the development of fibrosis. Murine flow cytometry and qRT-PCR studies mirrored the human ones, with increased T-helper cells and IL-4 in iLTS versus normal controls. Conclusion: CD3/CD4 + T-helper lymphocytes and the proinflammatory cytokine IL-4 are associated with iLTS. The association of a TH2 immunophenotype with iLTS is consistent with findings in other fibroinflammatory disorders. The murine results reveal that the inflammatory infiltrate precedes the development of fibrosis. However, human iLTS specimens with well-developed fibrosis also contain a marked chronic inflammatory infiltrate, suggesting that the continued release of IL-4 by T-helper lymphocytes may continue to propagate iLTS. Level of Evidence: NA. Laryngoscope, 2018.

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