P3‐4: THE TL1A/DR3 axis in the presence of TSLP induces steroid resistance of ILC2

Background and Aims: Corticosteroids are mainstay of treatment for patients with asthma. There are subset of patients with severe asthma who have persistent symptoms despite high dose corticosteroid treatment. There is evidence to suggest that type 2 innate lymphoid cells (ILC2s) are involved in the severe asthma with steroid-resistance. Precise mechanisms of steroid resistance induction on ILC2s has not been elucidated. The aim of this study is to address the role of DR3 (death receptor 3), expressed on ILC2s and its ligand, TL1A (tumor necrosis factor-like protein 1A), in the mechanism of steroid resistance induction. Methods: Enriched blood ILC2s, from mild asthmatics were stimulated with IL-2 (10 ng/mL) in combination with either TL1A (10 ng/mL)or TSLP (0.1 ng/mL), then treated with dexamethasone (10 9 M), to assess the steroid responsiveness of the TL1A/DR3 axis. Harvested cells were subject to immunofluorescence staining and enumerated by flow cytometry. Results and Conclusions: Dexamethasone significantly reduced IL-5 production by ILC2s in the IL-2 + TL1A (16.4 4.6 vs. 4.4 1.8%) or IL-2 + TSLP (27.7 7.9 vs. 15.2 5.7%) conditions. In contrast, no significant inhibitory effect was noted when TL1A and TSLP were added together. In conclusion the TL1A/DR3 axis in the presence of TSLP induces steroid resistance of ILC2.