Activation of Group 2 innate lymphoid cells after allergen challenge in asthmatics.

BACKGROUND: Group 2 innate lymphoid cells (ILC2) are effective producers of IL-5 and IL-13 during allergic inflammation and bridge the innate and adaptive immune response. ILC2 are increased in asthmatics compared to healthy controls. So far human data describing their phenotype during acute allergic inflammation in the lung is incomplete.

OBJECTIVES: This study aims to characterize and compare blood- and lung-derived ILC2 before and after segmental allergen challenge in mild to moderate asthmatic individuals with high blood eosinophil levels (≥300/μl).

METHODS: ILC2 were isolated from blood and bronchoalveolar lavage (BAL) before and after segmental allergen challenge. Cells were sorted by flow cytometry, cultured and analyzed for cytokine release or migration, and sequenced for RNA expression.

RESULTS: ILC2 were nearly absent in the alveolar space under baseline conditions but increased significantly after allergen challenge (P < 0.05) , whilst at the same time ILC2 numbers in blood were reduced (P<0.05). Prostaglandin D2 (PGD2 ) and CXCL12 levels in BAL correlated with decreased ILC2 numbers in blood (P = 0.004, respective P = 0.024). After allergen challenge several genes promoting type 2 inflammation were higher expressed in BAL compared to blood ILC2, while blood ILC2 remain unactivated.

CONCLUSION: ILC2 accumulate at the site of allergic inflammation and are recruited from the blood. Their transcriptional and functional activation pattern promote type 2 inflammation.