Human activated type 2 innate lymphoid cells are elevated in children with uncontrolled asthma

Background: Group 2 innate lymphoid cells (ILC2s) have been implicated in various immune disorders. We recently identified a subpopulation of ILC2s expressing CD45RO in the blood of adult patients suffering from T2 inflammation-mediated airways diseases. These activated CD45RO+ ILC2s displayed an inflammatory state, produced more IL-5/IL-13 than conventional ILC2s (cILC2s), and frequencies correlated with the level of disease control. Here, we identify and characterize these activated CD45RO ILC2s in the blood of children with uncontrolled asthma. Methods: We used flow cytometry, ELISA, and qPCR to characterize ILCs in the blood of in total n=24 adults and n=10 pediatric asthma patients and age-matched healthy controls (HC). We evaluated cell responses to ILC-activating cytokines and steroids. Asthma was classified according to asthma control questionnaire to controlled, partially controlled, and uncontrolled. Results: Whereas the frequencies of cILC2s and CD45RO+ ILC2 in the blood of adult and pediatric HC were similar, we found elevated levels of cILC2s in children with uncontrolled asthma and elevated frequencies of CD45RO+ ILC2s in uncontrolled asthma in both children and adults. Next to CD45RO expression, these activated ILC2s displayed reduced expression of CD45RA and CD62L, increased baseline production of IL-5/IL-13/IL-4, and increased expression of the lung homing marker CCR4. Finally, CD45RO+ ILC2s from asthmatic children produced significantly more IL-5/IL-13 upon activation than cILC2s and were resistant to steroids. Conclusion: CD45RO+ ILC2s play a significant role in driving the pathology of uncontrolled asthma and should be considered as a target for novel treatment options.