Identification of IL-17F/frequent exacerbator endotype in asthma

Area of Science:

• Immunology
• Respiratory Medicine
• Molecular Biology

Background:

• Severe asthma may involve T helper 17 (Th17) cytokine overexpression.
• Th17 cytokines can drive neutrophil recruitment in airways.

Purpose of the Study:

• To investigate IL-17-related cytokines in nasal and bronchial biopsies.
• To compare cytokine levels between controls, mild asthmatics (MAs), and severe asthmatics (SAs).
• To correlate cytokine expression with exacerbation rates in asthma patients.

Main Methods:

• Immunohistochemistry was used to examine inflammatory cells and IL-17A, IL-17F, IL-21, IL-22, and IL-23 expressing cells in bronchial and nasal biopsies.
• ELISA and immunohistochemistry measured IL-17F protein in bronchial tissue from fatal asthma cases.
• Immunofluorescence and confocal microscopy were employed for IL-17F colocalization studies.

Main Results:

• Severe asthmatics (SAs) showed higher numbers of neutrophils, IL-17A+, IL-17F+, and IL-21+ cells in bronchial biopsies compared to mild asthmatics (MAs).
• Nasal biopsies from SAs also had increased IL-17F+ and IL-21+ cells.
• Bronchial and nasal IL-17F+ cells correlated with neutrophils, exacerbation rates, and FEV1. Frequent exacerbators (FEs) exhibited elevated neutrophils, eosinophils, CD4+/CD8+ cells, and IL-17F+ cells.

Conclusions:

• IL-17-related cytokine expression is elevated in the airways of severe asthmatics prone to exacerbations.
• IL-17F appears to play a pathogenic role in frequent exacerbations of severe asthma.
• Elevated IL-17F levels can help differentiate between asthmatic and control groups and identify frequent exacerbators.