IL-17A from innate and adaptive lymphocytes contributes to inflammation and damage in cystic fibrosis lung disease

Matthias Hagner, Melanie Albrecht, Matteo Guerra, Peter Braubach, Olga Halle, Zhe Zhou-Suckow, Simone Butz, Danny Jonigk, Gesine Hansen, Carsten Schultz, Anna Maria Dittrich, Marcus A. Mall

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Elevated levels of interleukin (IL)-17A were detected in the airways of patients with cystic fibrosis (CF), but its cellular sources and role in the pathogenesis of CF lung disease remain poorly understood. The aim of this study was to determine the sources of IL-17A and its role in airway inflammation and lung damage in CF. Methods: We performed flow cytometry to identify IL-17A-producing cells in lungs and peripheral blood from CF patients and β-epithelial Na+ channel transgenic (Scnn1b-Tg) mice with CF-like lung disease, and determined the effects of genetic deletion of Il17a and Rag1 on the pulmonary phenotype of Scnn1b-Tg mice. Results: T-helper 17 cells, CD3+CD8+ T-cells, γδ T-cells, invariant natural killer T-cells and innate lymphoid cells contribute to IL-17A secretion in lung tissue, lymph nodes and peripheral blood of patients with CF. Scnn1b-Tg mice displayed increased pulmonary expression of Il17a and elevated IL-17Aproducing innate and adaptive lymphocytes with a major contribution by γδ T-cells. Lack of IL-17A, but not the recombination activating protein RAG1, reduced neutrophilic airway inflammation in Scnn1b-Tg mice. Genetic deletion of Il17a or Rag1 had no effect on mucus obstruction, but reduced structural lung damage and revealed an IL-17A-dependent macrophage activation in Scnn1b-Tg mice. Conclusions: We identify innate and adaptive sources of IL-17A in CF lung disease. Our data demonstrate that IL-17A contributes to airway neutrophilia, macrophage activation and structural lung damage in CF-like lung disease in mice. These results suggest IL-17A as a novel target for anti-inflammatory therapy of CF lung disease.

Original languageEnglish (US)
Article number200716
JournalEuropean Respiratory Journal
Volume57
Issue number6
DOIs
StatePublished - Jun 1 2021
Externally publishedYes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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