Persistence of asthma following avoidance of occupational allergens is associated with proTh2 myeloid dendritic cell activation

Background The natural history of asthma includes in some patients periods of disease remission, but the underlying mechanisms are unknown. Objectives We explored whether type 1 myeloid dendritic cell (mDC) dysfunction could be involved in the persistence of asthma, studying the controlled setting of occupational asthma (OA) after allergen avoidance. Methods We recruited 32 patients with OA to flour or latex ascertained by specific inhalation challenge and who were no longer exposed to the causal allergen. Leukapheresis was performed in each patient to isolate and characterize blood type 1 mDCs, and their functionality was studied in co-culture with allogeneic CD4+ T cells from controls. Results At follow-up, 11/32 patients (34%) were characterized by the absence of symptoms and nonspecific bronchial hyperresponsiveness to histamine and were considered to be cured. When compared to cured patients, mDCs from patients with persistent disease increased the production of IL-5 and IL-13 by CD4+ T cells, and upregulated programmed death-ligand 2 (PD-L2) upon allergen pulsing. In addition, IL-5 and IL-13 responses could be reversed by exogenous IL-12, as well as by PD-L2 blockade. Conclusions This study indicates that pro-Th2 features of mDCs correlate with disease activity in asthma after cessation of exposure to the causal allergen. The findings also highlight that the Th2 programming by DCs is flexible and partly mediated by PD-L2.