ProTh2 function of myeloid dendritic cells in persistent occupational asthma after cessation of exposure

Introduction Asthma resolves in only a minority of patients with occupational asthma (OA) despite complete avoidance of the causal agent. We aimed at exploring whether mDC function contributed to persistent disease after cessation of exposure to occupational allergens. Material and methods We recruited 32 patients with OA to flour or latex ascertained by specific inhalation challenge who were no longer exposed to the causal allergen. At follow-up, cure was defined by the absence of asthma symptoms, use of asthma medication, and nonspecific bronchial hyperresponsiveness to histamine (PC20>8 mg/mL). A buffy coat was obtained from each patient to isolate and characterize mDCs, and their functionality was studied in co-culture with CD4+ T cells from control subjects. Results When compared to cure (n=11), asthma persistence (n=21) was associated with higher expression of thymic stromal lymphopoietin receptor (TSLPR) (58.8 ± 16.9% vs 28.4 ± 8.4 %, P<0.001) and lower expression of ICOS-ligand (13.9 ± 9.4% vs 25.9 ± 14.8 %, P=0.011) on mDCs. Upon allergen pulsing in vitro , mDCs from patients with persistent asthma upregulated the production of IL-5 (from 0.48 ± 0.4 ng/mL to 1.16 ± 0.5 ng/mL, vs from 0.41 ± 0.5 ng/mL to 0.5 ± 0.6 ng/mL, P=0.02) and IL-13 (from 0.23 ± 0.1 ng/mL to 0.59 ± 0.3 ng/mL vs from 0.17 ± 0.1 ng/mL to 0.31 ± 0.2 ng/mL, P=0.02) by co-cultured CD4+ T cells. Unlike mDCs from cured patients, they also upregulated programmed death-ligand 2 (35.04 ± 6.3 % vs 27.2 ± 11.8 % P=0.04). Conclusions These data show that in patients with occupational asthma, pro-allergic functionality of mDCs correlates with disease activity after cessation of exposure to the causal allergen.