Interleukin (IL)-5 Receptor Expression on Blood Neutrophils (Pmns)

We previously demonstrated that IL-5R expression is a feature of blood and airway PMNs. This led to speculation that biologics targeting IL-5/IL-5R may benefit in part through their ability to target PMNs. It is unknown how the level of expression of IL-5R compares on PMNs and eosinophils. Numerous isoforms of IL-5R have been described which may impact responsiveness to IL-5. We investigated differences in receptor expression and isoform utilization on PMNs and eosinophils in normal and allergic cohorts. PMNs were obtained from control and allergic subjects. Expression of IL-5R was quantified via flow cytometry gated to distinguish PMNs from eosinophils. Structural differences in the IL-5R were assessed via qPCR using isoform-specific primers. Expression of CD125 on PMNs was variable and this was not impacted by the presence of an allergic diagnosis. However, in the control cohort similar levels of CD125 expression were observed on eosinophils (20.4%) and PMNs. (21.6%). This was in contrast to the allergic cohort where significantly higher expression was observed on PMNs (20.6%) compared to eosinophils (11.3%; p<0.01). Frequent individuals (∼30-50%) were identified displaying different receptor isoforms on their PMNs and eosinophils. Expression of IL-5R on PMNs is similar to that on eosinophils and is independent of allergic disease diagnosis. Reduced expression of CD125 on eosinophils in the allergic cohorts may represent their selective recruitment to the inflamed airway. Selective targeting of eosinophils as opposed to PMNs by IL-5 (or by IL-5R-targeting biologics) could occur based upon the different structural isoforms observed on these 2 granulocyte populations.