SAT0029 Dectin-1 Mediates Aberrant Innate and Adaptive Immune Response in Patients with Systemic Lupus Erythematosus

Background Dectin-1 is a c-type lectin receptor that signals via syk and is involved in anti-fungal immunity. Dectin-1 was found to trigger experimental inflammatory arthritis, and likely play a role in the pathogenesis of some autoimmune diseases. Objectives To examine (1) dectin-1 expression on circulating CD14+ monocytes in patients with systemic lupus erythematosus (SLE), (2) the effects of dectin-1 stimulation in ROS production by lupus monocytes and (3) syk signaling and cytokine profile of dectin-1 stimulated lupus monocyte-derived dendritic cells (MDDCs). Methods SLE patients with active and inactive diseases and healthy subjects were recruited. MDDCs were derived from peripheral monocytes in the presence of IL-4 and GM-CSF. Dectin-1 agonists including curdlan, zymosan and toll-like receptor agonists Pam 3 CSK 4 (TLR2) and LPS (TLR4) were used to stimulate monocytes and/or MDDCs. Dectin-1, ROS and phosphorylated-syk (p-syk) were measured by flow cytometry. Cytokine profile was measured by and multi-bead immunoassay. Results The percentage of dectin-1 expressing monocytes was significantly lower in active SLE patients (64.5±24.3%) compared to inactive patients (89.6±7.2%) and healthy controls (91.7±9.5%) (both p Conclusions Active SLE patients had significantly lower circulating dectin-1 expressing CD14+ monocytes which produced comparable level of ROS upon stimulation compared to inactive patients and healthy subjects. Dectin-1 agonists led to activation, maturation and higher p-syk activation in SLE MDDCs. Concomitant dectin-1 and TLR2 stimulation induced production of Th17 promoting cytokines, among which IL-1β and IL-6 were significantly higher in SLE compared to normal MDDCs. Disclosure of Interest None declared