Background
Children with severe therapy-resistant asthma (STRA) have poor control despite maximal therapy. The pattern of airway inflammation in severe disease may therefore be less steroid sensitive. Innate lymphoid cells (ILCs) are immune cells of lymphoid morphology that do not express typical antigen receptors but mirror the functions of T cells. They are classified into three groups. ILC2s express CD127 and CRTH2, secrete Th2 cytokines, express GATA3 and are induced by IL-33 which is steroid resistant and increased in paediatric STRA. I hypothesised that airway ILC2s are increased in STRA and are steroid resistant, thus contributing to disease pathology. I characterised ILC2s in induced sputum (IS), broncho-alveolar lavage (BAL) and peripheral blood (PBMC) in children with STRA compared to non-asthmatic controls and investigated their response to systemic steroids. Methods BAL, PBMCs and IS were obtained from 18 STRA children and 16 with chronic inflammation (CI) undergoing a clinically indicated bronchoscopy. IS was obtained in an additional 13 children with STRA and 6 with CI. Cells were analysed by multi-parametric flow cytometry for ILC and Th2 markers. Assessments of sputum ILCs were performed in STRA before and after systemic steroids. In vitro cultures of PBMCs were undertaken to determine ILC and T cell responses to allergen and steroids. Results ILC2s were identified in IS from STRA, but not CI, and were significantly higher in BAL and sputum than PBMCs in STRA. Th2 cells were ten-fold higher than ILC2s in all compartments. Sputum ILC2s decreased following systemic steroids and PBMC cultures showed a significant reduction in ILC2s with steroids. Conclusion ILC2s were elevated in children with STRA and were more abundant in airways than peripherally. However, Th2 cells were the predominant lymphoid airway cell type. Unlike IL-33, ILC2s were steroid sensitive thus their contribution in mediating severe, steroid resistant disease remains uncertain