Interplay of NLRC4/NLRP3 inflammasomes and Fc-?-Receptors on CD1c+ DC Associates with Pathogenic IFN?+IL17+ T cells and RA Severity

Deregulated myeloid cells infiltrating to the joints likely contribute to rheumatoid arthritis (RA) pathogenesis through multiple mechanisms, including the secretion of proinflammatory cytokines and the induction of pathogenic adaptive Th17 cells, that mediate joint damage. However, the individual contribution of specific myeloid subsets such as CD1c+ and CD141+ conventional dendritic cells (cDC) to RA development and progression has been poorly studied and remains unclear. In particular, the potential molecular mechanisms specifically affecting CD1c+ cDCs in RA patients and their functional implications have not been characterized. Using RNA-seq, multiparametric flow cytometry and in vitro functional assays, we compared in parallel transcriptional, phenotypical and functional characteristics of monocytes, CD1c+ and CD141+ cDCs from the blood and synovial fluid of RA patients. Overall design: We performed RNA sequencing using RNA from Monocytes, Dendritic Cd1c+ and Dendritic Cd141 cells obtained from blood/sinovial fluid of Rheumatoid Arthritis versus healthy/CPPD matched controls.