IL-25R+ circulating fibrocytes are increased in asthma and correlate with fixed airflow limitation

Introduction Interleukin (IL)-25 is a T helper (Th) type-2 cytokine implicated in the pathogenesis of asthma. Fibrocytes are progenitor cells that can migrate into circulation and inflamed bronchial epithelium. Objectives We aim to test the hypothesis that circulating fibrocytes may be the novel cellular targets of IL-25 and the recruitment of IL-25R(+) circulating fibrocytes may correlate with asthmatic airway obstruction. Methods By using flow cytometry analysis, IL-25R(+) fibrocytes (i.e., IL-17RB(+) fibrocytes) in the freshly isolated peripheral blood mononuclear cells (PBMCs) from 15 control subjects and 35 patients with asthma were enumerated and compared. Enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of IL-25. Results We found the percentage of total and IL-25R(+) (IL-17RB(+)) fibrocytes in PBMCs was significantly increased in patients with asthma when compared with control subjects. Subgroup analysis further showed that the percentage of circulating total and IL-25R(+) fibrocytes in PBMCs was markedly increased in asthma patients with severe-to-very severe fixed airflow limitation. Furthermore, IL-25R(+) circulating fibrocytes in asthma patients were shown to significantly correlate with forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), FEV1% predicted, blood eosinophils, serum IgE and plasma IL-25 levels. Conclusion We concluded that circulating fibrocytes are the novel potential cellular targets of IL-25. IL-25R(+) fibrocytes are increased in asthma patients. Increased proportions of IL-25R(+) fibrocytes predict a distinct asthma phenotype with fixed airflow limitation. Biological therapy-targeting IL-25-fibrocytes axis may offer great promise for the control of asthma patients with severe airway remodelling and obstruction.

Automated summary

This study revealed that circulating fibrocytes may be novel cellular targets of IL-25 in asthma patients, and the recruitment of IL-25R(+) fibrocytes is correlated with asthmatic airway obstruction. Increased proportions of IL-25R(+) fibrocytes predict a distinct asthma phenotype with fixed airflow limitation. Targeting the IL-25-fibrocytes axis in biological therapy holds promise for controlling asthma patients with severe airway remodeling and obstruction.