TY - JOUR T1 - Rapamycin reduces eosinophilopoiesis through suppression of IL-5 production by bone marrow ILC2s JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2021.PA859 VL - 58 IS - suppl 65 SP - PA859 AU - Emma Boberg AU - Julie Weidner AU - Carina Malmhäll AU - Jenny Calvén AU - Carmen Corciulo AU - Madeleine Rådinger Y1 - 2021/09/05 UR - http://erj.ersjournals.com/content/58/suppl_65/PA859.abstract N2 - Background: Type 2 innate lymphoid cells (ILC2s) are regulators of type 2 inflammation in asthma. The mechanistic target of rapamycin (mTOR) inhibitor, rapamycin, has previously been reported to suppress inflammatory properties of lung ILC2s in an interleukin (IL)33-induced asthma mouse model. IL-33 induces bone marrow eosinophilia and we aimed to determine the anti-inflammatory properties of rapamycin with a focus on bone marrow eosinophils and ILC2s.Methods: Mice were pre-treated intraperitoneally with rapamycin one hour before receiving intranasal doses of recombinant IL-33 and were compared to control mice. IL-33-stimulated bone marrow cultures were treated with or without rapamycin and type 2 inflammation was determined by measuring IL-5+ ILC2s. Flow cytometry was used to characterize eosinophils and to measure the activity of the mTOR complex in ILC2s.Results: A significant reduction in eosinophil numbers with a lower mean fluorescence intensity of the IL-33 receptor ST2 was observed in the rapamycin+IL-33 group compared to IL-33 only. The total number of ILC2s was unchanged. Phosphorylation of Rps6, indicative of mTOR activity, was increased in ILC2s from the IL-33 only group and a reduced activity was observed in the rapamycin+IL-33 group. Furthermore, IL-5+ ILC2s decreased in bone marrow cultures with rapamycin+IL-33 compared to IL-33 only.Conclusion: Our data indicate that the mTOR pathway is essential for type 2 inflammation caused by bone marrow IL-5+ ILC2s in IL-33-induced eosinophilic inflammation. This mechanism can influence eosinophilopoiesis and the recruitment of eosinophils to sites of inflammation that might have implications for asthma pathogenesis.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA859.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -