348 Dectin-1 on monocytic cells mediates aberrant innate and adaptive immune responses in patients with systemic lupus erythematosus

• Published in: Lupus science & medicine Vol. 4; no. Suppl 1; p. A152
• Main Authors: Mok, MY, Lam, KY, Luk, D, Lo, Y
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.03.2017
• ISSN: 2053-8790
• DOI: 10.1136/lupus-2017-000215.348

Background and aimsDectin-1 is a c-type lectin like 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. This study aimed to examine dectin-1 expression and function of circulating CD14+ monocytes and monocyte-derived dendritic cells (MDDCs) in patients with systemic lupus erythematosus (SLE)MethodsSLE patients with active and inactive diseases and healthy subjects were recruited. Dectin-1 agonists including curdlan, zymosan and toll-like receptor agonists Pam3CSK4 (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.ResultsDectin-1 expressing monocytes was significantly lower in active SLE patients compared to inactive patients and healthy controls. The absolute count of dectin-1 expressing monocytes correlated significantly and inversely with SLEDAI, anti-dsDNA antibody level and C4. Despite this, ROS production upon stimulation by dectin-1 agonists was comparable. Stimulation of dectin-1 led to activation and maturation of MDDCs. SLE MDDCs showed higher p-Syk activation compared to normal MDDCs upon dectin-1 stimulation. Curdlan-stimulated MDDCs produced higher levels of IL-1β, IL-23 and TNF-α. Adding TLR2 agonist to curdlan, SLE MDDCs produced significantly higher level of IL-1β compared to normal MDDCs.ConclusionsActive SLE patients had significantly lower circulating dectin-1 expressing monocytes which produced comparable level of ROS compared to inactive patients and healthy subjects. Dectin-1 agonists led to significantly higher Th17 promoting cytokines upon co-stimulation with TLR2 in SLE MDDCs.