NLRC4-mediated activation of CD1c(+) DC contributes to perpetuation of synovitis in rheumatoid arthritis

The individual contribution of specific myeloid subsets such as CD1c(+) conventional DC (cDC) to perpetuation of rheumatoid arthritis (RA) pathology remains unclear. In addition, the specific innate sensors driving pathogenic activation of CD1c(+) cDC in patients with RA and their functional implications have not been characterized. Here, we assessed phenotypical, transcriptional, and functional characteristics of CD1c(+) and CD141(+) cDC and monocytes from the blood and synovial fluid of patients with RA. Increased levels of CCR2 and the IgG receptor CD64 on circulating CD1c(+) cDC was associated with the presence of this DC subset in the synovial membrane in patients with RA. Moreover, synovial CD1c(+) cDC are characterized by increased expression of proinflammatory cytokines and high abilities to induce pathogenic IFN-γ(+)IL-17(+)CD4(+) T cells in vitro. Finally, we identified the crosstalk between Fcγ receptors and NLRC4 as a potential molecular mechanism mediating pathogenic activation, CD64 upregulation, and functional specialization of CD1c(+) cDC in response to dsDNA-IgG in patients with RA.