Background In innate immunity, inflammasomes, which are multiple protein complexes, activate inactive procaspase-1 into active caspase-1. Cytokines such as IL-1β, IL-18, IL-33 and IL-1F7 are converted into their active forms by caspase-1. Although the pathogenesis of Behcet’s Disease (BD) is still unclear, both innate and adaptive immunity participate with a Th1/Th17 response. Previously, activation of toll-like receptors (TLRs) on monocyte and neutrophils are reported, however the role of other innate immune system receptors (like NLR and RLR) and inflammasome in BD is not sufficiently investigated.
Objectives In this study, inflammasome functions were investigated in dendritic cells (DC) of BD patients through the activation of two different pattern-recognition receptors: “RIG-1 like receptors (RLR) and “NOD-like” receptors (NLR).
Methods Sixteen active BD patients with mucocutaneous lesions (F/M: 9/7, mean age: 38±13 years) and 17 healthy controls (HC) (F/M: 5/12, mean age: 35±8 years) were included in the study. Peripheral blood mononuclear (PBMN) cells were isolated and dendritic cells (DC) were generated from monocytes in a dendritic cell maturation medium containing GM-CSF, IL-4, TNF-α, IL-1β, IL-6 and PGE2. DCs were activated by RLR and NLR ligands. Caspase-1 activation was investigated by flow cytometry using a Caspase 1 FLICA™ Kit. IL-1β, IL-6, TNF-α, IFN-α and IL-18 were measured by ELISA and intracellular p38 and RIP2 staining weredetermined by flow cytometry.
Results Caspase-1 activation was similar in BD compared to HC (NOD1; BD: 1.5% vs HC: 1.9%, NOD2; BD: 1.7% vs HC: 1.5%, RIG1; BD: 1.7% vs HC: 1.5%, p>0.05 for all of them). The levels of IL-1β, TNF-α, IL-6 and IFN-α were also similar in the supernatants of NOD1/2 and RIG2-activated DC cultures of BD patients compared to HC. Only IL-18 levels were significantly lower after NOD2 activation (BD: 18 pg/ml vs HC: 46 pg/ml, p=0.017), similarly p38 and RIP2 expressions were also lower in BD (p38: BD: 1.3% vs. HC: 1.8% and RIP2: BH: 1.1% vs. HC: 1.9%, p=0,037 and p=0.018, respectively).
Conclusions In Behcet’s disease, after NOD1/NOD2 and RIG-1 activations, inflammasome seem to be activated normally in DCs, except mildly lower IL-18, p38 and RIP2 stimulations after NOD2 ligands. This observation suggests that caspase-1 independent pathways such as TLRs may be more prominent for innate activation in antigen-presenting cells in BD pathogenesis.
Disclosure of Interest None Declared
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