Activation of group 2 innate lymphoid cells after allergen challenge in asthmatic patients

Abstract

Group 2 innate lymphoid cells (ILC2s) are effective producers of IL-5 and IL-13 during allergic inflammation and bridge the innate and adaptive immune responses. ILC2 numbers are increased in asthmatic patients compared with healthy control subjects. Thus far, human data describing their phenotype during acute allergic inflammation in the lung are incomplete. This study aims to characterize and compare blood- and lung-derived ILC2s before and after segmental allergen challenge in patients with mild-to-moderate asthma with high blood eosinophil counts (≥300cells/μL). ILC2s were isolated from blood and bronchoalveolar lavage (BAL) fluid before and after segmental allergen challenge. Cells were sorted by means of flow cytometry, cultured and analyzed for cytokine release or migration, and sequenced for RNA expression. ILC2s were nearly absent in the alveolar space under baseline conditions, but numbers increased significantly after allergen challenge (P<.05), whereas at the same time, ILC2 numbers in blood were reduced (P<.05). Prostaglandin D2 and CXCL12 levels in BAL fluid correlated with decreased ILC2 numbers in blood (P=.004, respective P=.024). After allergen challenge, several genes promoting type 2 inflammation were expressed at greater levels in BAL fluid compared with blood ILC2s, whereas blood ILC2s remain unactivated. ILC2s accumulate at the site of allergic inflammation and are recruited from the blood. Their transcriptional and functional activation pattern promotes type 2 inflammation.