IL-13⁺ Type 2 Innate Lymphoid Cells Correlate with Asthma Control Status and Treatment Response

Type 2 innate lymphoid cells (ILC2s) have been shown to produce large amounts of type 2 cytokines in a non-antigen-specific manner. These cytokines act upstream and downstream of ILC2 and are increasingly common in asthma drug development, thus warranting a closer investigation of the mechanism-related clinical manifestations of ILC2 in the selection of patients with asthma. We hypothesized that IL-13⁺ILC2s in the circulation might correlate with asthma control status as a result of persistent T-helper cell type 2 (Th2) inflammation in the lung. Furthermore, we aimed to explore ILC2s' responsiveness to glucocorticoid. The percentages of ILC2s and IL-13⁺ILC2s in different asthma subgroups were checked, and correlation analyses between ILC2s and asthma-related clinical parameters were performed. Dexamethasone treatments in ILC2s and Th2 cells were performed to clarify their response properties. ILC2s were identified as a Lin^-CD45^hiIL-7Rα⁺CRTH2⁺ cell population distinct from human peripheral blood mononuclear cells. Frequencies of ILC2s were increased dramatically in those with asthma (0.04 ± 0.02%) compared with healthy donors (0.025 ± 0.011%). The percentages of IL-13⁺ILC2s were significantly higher in patients in the uncontrolled group (49.7 ± 16.9%) and partly controlled groups (30.8 ± 13.1%) than in those in the well-controlled group (16.7 ± 5.9%) and healthy control subjects (18.7 ± 8.7%). Effective treatment of uncontrolled IL-13⁺ILC2-positive patients with asthma resulted in dynamic modulation of IL-13⁺ILC2 levels back to baseline. ILC2s were more resistant to glucocorticoid than Th2 cells in vitro. ILC2s are strong responders to IL-25/IL-33 stimulation. IL-13⁺ILC2s show a positive correlation with patient asthma control status and are more resistant to glucocorticoid than Th2 cells in humans.