Background: Type 2 biologics represent a novel strategy for the treatment of severe asthma and potently reduce exacerbations and oral corticosteroids (OCS) use. Type 2 innate lymphoid cells (ILC2s) have been suggested as crucial drivers of eosinophilic airway inflammation. While the clinical effects of type 2 biologics have been well studied, the effects on the ILC compartment have not been explored.

Methods: Peripheral blood mononuclear cell (PBMC) samples and extensive clinical data were collected from 40 patients with severe asthma at baseline and after 4 and 12 months of mepolizumab (n=33) or dupilumab (n=7) treatment. PBMC were analysed using 24-parameter flow cytometry.

Results: Mepolizumab treatment led to a significant decrease in blood eosinophils (both p<0.0001), OCS use (p<0.03, p=0.0005), exacerbations (both p<0.0001), FeNO (p<0.03, p=0.14) and an increased FEV1 (p=0.12, p<0.03) at 4 and 12 months, respectively. Clinical effects were paralleled by a significant increase in blood ILC2 frequency between baseline and 4 and 12 months of treatment within the ILC (p=0.001, p<0.02) and the total lymphocyte compartment (p<0.02, p<0.04). Moreover, we observed a significant increase of mature CD117^low ILC2s that have been shown to produce higher levels of type 2 cytokines as compared to the CD117^high ILC2 subset. The frequency of ILC2 and CD117^low ILC2 was also increased after 4 months (p<0.016, p=0.31) and 12 months (p<0.047, p<0.016) of dupilumab treatment.

Conclusion: The increased frequency of circulating ILC2 during mepolizumab and dupilumab treatment could be the result of reduced migration of ILC2 to the lung.