POS0367 NLRC4 AND FC-γ-R CROSSTALK ON CD1C+ DENDRITIC CELLS DIFFERENTIALLY CONTRIBUTES TO RHEUMATOID ARTHRITIS IMMUNOPATHOLOGY

Background: Rheumatoid arthritis (RA) is an autoimmune disorder in which Th17 cells, B cells and inflammatory cytokines (1-3) contribute to joint tissue damage, however the role of specific myeloid populations immunopathogenesis RA remains unclear. Objectives: To address this question, we studied transcriptional, phenotypical functional characteristics monocytes (Mo), CD1c + CD141 conventional dendritic (cDC) from patients. Methods: Frequencies maturation patterns Lin-CD14-HLADR+ plasmacytoid (CD11c-), CD1c+ CD141+ cDC (CD11c+) subsets CD14+ Mo n=25 patients at baseline were analyzed by multicolor flow cytometry. In addition, longitudinal studies on evolution these after treatment initiation conducted a smaller group Moreover, total sorted peripheral blood n=4 untreated healthy individuals synovial fluid n=3 chondrocalcinosis Differential transcriptional within each population RNAseq. Functional validation targets performed vitro with isolated form synoviual Finally, silencing expression NLRC4 NLRP3 CD1c+cDCs was siRNAs. Results: Both (p=0.0001) (p=0.0008) cDCs significantly depleted enriched patients, but proportions more recovered associated improved clinical parameters. increased levels IgG-Fc receptor CD64 higher DAS28 (p=0.0002). differential circulating characterized genes linked toll-like receptor, Fc-receptor, inflammasome pathways elevated CCR2 (p=0.016), while transcribed interferon-related genes. Importantly, Hi proinflammatory such as IL1-β, CCL3 IL-8, actively expressed mediator caspase 1 effective activating pathogenic IFNγ IL-17 CD4 T than (p=0.0019). These profiles could be artificially induced stimulating dsDNA presence IgGs dependent inflammasome. Conclusion: Our data provides novel insights about activation contributing pathogenesis identifies new sensors that represent therapeutic target treat RA. References: [1]Alvandpur N, Tabatabaei R, Tahamoli-Roudsari A, Basiri Z, Behzad M, Rezaeepoor et al. Circulating IFN-gamma producing CD4+ IL-17A HLA-shared epitope ACPA may characterize response therapy rheumatoid Human immunology. 2020. [2]Nistala K, Adams S, Cambrook H, Ursu Olivito B, de Jager W, plasticity human driven environment. Proceedings National Academy Sciences United States America. 2010;107(33):14751-6. [3]Chapuy-Regaud Nogueira L, Clavel C, Sebbag Vincent Serre G. IgG subclass distribution arthritis-specific autoantibodies citrullinated fibrin. Clinical experimental 2005;139(3):542-50. Disclosure Interests: None declared