CXCL4 Exposure Potentiates TLR-Driven Polarization of Human Monocyte-Derived Dendritic Cells and Increases Stimulation of T Cells

• DOI: 10.4049/jimmunol.1602020
• Publication Date: 2017-05-18T00:30:19Z
• Authors: Sandra C Silva-Ca...; Alsya J Affandi; Lotte Spel; Marta Cossu; Joel A G van Roon; Marianne Boes; Timothy R D J Rad...
• Keywords: Monocyte

Abstract Chemokines have been shown to play immune-modulatory functions unrelated steering cell migration. CXCL4 is a chemokine abundantly produced by activated platelets and immune cells. Increased levels of circulating are associated with immune-mediated conditions, including systemic sclerosis. Considering the central role dendritic cells (DCs) in activation, this article we addressed effect on phenotype function monocyte-derived DCs (moDCs). To end, compared innate adaptive responses moDCs those that were differentiated presence CXCL4. Already prior TLR- or Ag-specific stimulation, CXCL4-moDCs displayed more matured phenotype. We found exposure can sensitize for TLR-ligand responsiveness, as illustrated dramatic upregulation CD83, CD86, MHC class I response TLR3 TLR7/8-agonists. Also, observed markedly increased secretion IL-12 TNF-α exclusively upon stimulation polyinosinic-polycytidylic acid, R848, CL075 ligands. Next, analyzed modulating DC-mediated T activation. strongly potentiated proliferation autologous CD4+ CD8+ production IFN-γ IL-4, an Ag-independent manner. Although internalization Ag was comparable moDCs, processing impaired. Yet, these potent at stimulating responses. Together our data support may contribute dysregulation through modulation DC differentiation.