IL-5Rα expression on airway neutrophils in children with treatment-refractory asthma

RATIONALE: Asthma is a chronic inflammatory lung disorder affecting 9% of children in the United States, a subset of whom have treatment-resistant disease and experience significant morbidity. Our understanding of the pathophysiologic basis of treatment-resistant asthma remains incomplete. The emphasis of emerging biologic treatments has been on a Th2-driven eosinophilic phenotype. While IL-5 is a canonical Th2 cytokine whose receptor is classically thought to be expressed by eosinophils and basophils, recent work revealed unexpectedly that CD125 (IL-5Rα) is also expressed on lung neutrophils in a murine model of influenza A infection. This prompted us to evaluate for CD125 on lung neutrophils in a cohort of severe asthmatic children.

METHODS: Children with treatment-refractory asthma (n=48) underwent diagnostic bronchoscopy and collection of bronchoalveolar lavage fluid (BALF). BALF granulocytes including SSC^highCD45⁺CD66b⁺Siglec8^- neutrophils and SSC^highCD45⁺CD66b^+/-Siglec8⁺ eosinophils were evaluated for surface and intracellular expression of CD125.

RESULTS: CD125 expression was detected on the cell surface of BALF neutrophils (median 26.9% CD125+ cells), with greater expression on eosinophils (median 63.7% CD125+ cells). Intracellular CD125 was detected on 84.8% of neutrophils and 93.7% of eosinophils.

CONCLUSIONS: Our data demonstrate the novel finding of CD125 expression as a consistent feature of both airway neutrophils and eosinophils in children with severe asthma. This finding has important implications for emerging therapeutic interventions directed against the IL-5/IL-5Rα axis. Further studies are needed to understand the effects of IL-5 mediated signaling in neutrophils; define the relevant factors that lead to CD125 expression on neutrophils; and address the effects of IL-5 targeted therapies on airway CD125+ neutrophils.