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.