Molecular Signatures of Dendritic Cell Activation upon TNF Stimulation: A Multi-Omics Study in Rheumatoid Arthritis.

Dendritic cells (DCs) play a central role in the immunopathogenesis of rheumatoid arthritis (RA), yet their regulation by tumor necrosis factor alpha (TNF) and associated receptors remains poorly characterized. We applied a single-cell multi-omics approach (CITE-seq) to profile peripheral blood mononuclear cells (PBMCs) from RA patients and healthy donors, before and after in vitro TNF stimulation. Using integrated analysis of surface protein expression and transcriptomic data, we focused on phenotypic and transcriptional changes in dendritic cell populations. DCs from RA patients exhibited elevated surface expression of CD14 and CD16, indicative of an inflammatory phenotype, and showed marked responsiveness to TNF. Upon stimulation, RA-derived DCs upregulated genes involved in antigen presentation (, ), lymph node migration (, ), and inflammation (, ) whereas such activation was absent in healthy controls. Our data reveal a TNF-responsive, pro-inflammatory transcriptional program in dendritic cells from RA patients and underscore the relevance of the TNF receptor profile in shaping DC function. These findings provide new insights into the immunobiology of RA and identify dendritic cells as potential targets for personalized immunomodulatory therapy.