The findings suggested a potential benefit for individualized occupational therapy. It should be tailor made with individual needs and continued for sustained effectiveness.

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BackgroundDectin-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.ObjectivesTo 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).MethodsSLE 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 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.ResultsThe 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<0.001). The absolute count of dectin-1 expressing monocytes correlated significantly and inversely with SLEDAI (r=-0.40, p<0.001), anti-dsDNA antibody level (r=-0.29, p=0.004), C3 (r=0.35, p=0.001) and C4 (r=0.24, p=0.02). Despite this, ROS production upon stimulation by dectin-1 agonists was comparable between these 3 groups. Stimulation of dectin-1 led to activation and maturation of MDDCs with upregulation of HLA-DR and CD86 (all p<0.001). SLE MDDCs showed higher p-syk activation compared to normal MDDCs upon dectin-1 stimulation (6.0±2.0 vs 2.8±1.0%, p<0.001). 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 (327.1±51.5 vs 125.3±88.5, p=0.009) and IL-6 (median 39.8 vs 21.7, p=0.03) compared to normal MDDCs. Combination of TLR4 agonist and curdlan induced IL-12 and TNF-α in normal MDDCs whereas lupus MDDCs produced predominant IL-6 and TNF-α.ConclusionsActive 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 InterestNone declared

BackgroundGeneration of tolerogenic dendritic cells (DCs) has been extensively studied using cytokine, growth factor, genetic engineering and pharmacological methods. Tolerogenic DCs are increasingly explored as cell-based therapy in murine model of autoimmune diseases and may have potential therapeutic implications in the treatment of systemic lupus erythematosus (SLE) that is characterised by dysregulated innate and adaptive immune responses.ObjectivesIn this study, we generated alternatively activated DCs (aaDCs) from SLE patients and healthy subjects and examined their immunoregulatory properties in vitro.MethodsaaDCs were generated by treating monocyte-derived DCs by combination of 1,25 dihydroxyvitamin D(3) (vitD3) and dexamethasone followed by lipopolysaccharide-induced maturationResultsLupus aaDCs were found to acquire semi-mature phenotype that remained resistant to immunostimulatory effect of sCD40L, CpG-DNA and SLE serum. These cells produced low level of IL-12 but high level of IL-10. They had attenuated allostimulatory effect on T cell activation and proliferation comparable to normal aaDCs and demonstrated differential immunomodulatory effects on naïve and memory T cells. These aaDCs were capable of inducing IL-10 producing regulatory T effectors from naïve T cells whereas they modulated cytokine profile with suppressed production of IFN-γ and IL-17 by co-cultured memory T cells with attenuated proliferation. The tolerogenicity of aaDCs was shown to be superior than those generated using vitD3 alone in lupus patients. aaDCs expressed lower level of RelB but apoptosis of DCs and IL12/IL-10 imbalance were not found to account for their tolerogenicity.ConclusionsOur data suggested that combination of vitD3 and dexamethasone represented a feasible method in the generation of tolerogenic DCs from SLE patients.Disclosure of InterestNone declared