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348 Dectin-1 on monocytic cells mediates aberrant innate and adaptive immune responses in patients with systemic lupus erythematosus
  1. MY Mok1,
  2. KY Lam2,
  3. D Luk2 and
  4. Y Lo2
  1. 1City University of Hong Kong, Department of Biomedical Sciences, Hong Kong, Hong Kong S.A.R
  2. 2University of Hong Kong, Department of Medicine, Hong Kong, Hong Kong S.A.R

Abstract

Background and aims Dectin-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)

Methods SLE 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.

Results Dectin-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.

Conclusions Active 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.

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