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

The Journal of Immunology : Official Journal of the American Association of Immunologists
Sandra C Silva-CardosoTimothy R D J Radstake

Abstract

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

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Citations

Jan 25, 2020·International Journal of Molecular Sciences·Marlene Bravo-ParraVerónica Mata-Haro
Jan 24, 2020·Clinical and Experimental Immunology·T CarvalheiroW Marut
Jun 6, 2020·European Journal of Immunology·Sandra C Silva-CardosoAridaman Pandit
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Oct 13, 2020·Frontiers in Immunology·Sandra C Silva-CardosoAridaman Pandit
Nov 12, 2017·Immunology Letters·Alsya J AffandiWioleta Marut
Oct 15, 2020·Transfusion Medicine Reviews·Amal MaouiaJohn W Semple

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