Trained immunity and tolerance in innate lymphoid cells, monocytes, and dendritic cells during allergen-specific immunotherapy

Background Despite the efficacy of allergen-specific immunotherapy (AIT), role trained immunity and tolerance in this process has not been elucidated. Objective Here, we have performed a comprehensive longitudinal analysis systemic innate immune cell repertoire during course AIT. Methods Patients with allergy received standard preseasonal subcutaneous AIT allergoids to birch and/or grass. Healthy controls were monitored without any intervention. Flow cytometry lymphoid (ILC), natural killer cell, monocyte dendritic (DC) subsets was at baseline, 3 months (birch season), 6 (grass seasons), 12 after therapy patients or similar seasonal time points controls. Additional analyses third-year grass season. Results We observed durable decrease group 2 ILCs an increase 1 AIT, dynamic changes their composition. found that expansion CD127+CD25++ clusters caused shifts heterogeneity ILCs. In addition, development CD127+CD25++c-Kit+ ILC clusters. Moreover, number intermediate monocytes parallel reduction nonclassical first year Classical presented significant allergy, but reduced HLA-DR++ Finally, plasmacytoid DCs CD141+ myeloid individuals whereas CD1c+ Conclusion induces composition circulating cells brings them level healthy individuals. Monitoring ILCs, monocytes, might serve as novel biomarker strategy.