Background/Purpose:

Accelerated atherosclerosis is the leading cause of death in systemic lupus erythematosus (SLE). How SLE promotes accelerated atherosclerosis remains elusive. The purpose of this study was to show that actors of SLE pathogenesis – such as CD4+ T cells and plasmacytoid dendritic cells (pDCs) – contribute to atherosclerosis.

Methods: Internal carotid wall thickness was prospectively assessed, as a measure of atherosclerosis, in 51 SLE patients asymptomatic for cardiovascular disease and 18 controls. The expression of CXCR3, a chemokine receptor involved in tissue migration of T cells, on peripheral blood mononuclear cells was measured. We analyzed in vitro the effect of pDCs-derived IFN-α production on CD4+ T cells and on CXCR3 ligands production by endothelial cells. Eventually, the impact of TLR-9 stimulated pDCs on atherosclerosis development was studied in a mouse model

Results:

SLE patients displayed an increased frequency of pro-inflammatory CD4+ T cells expressing CXCR3 that correlates with subclinical atherosclerosis. Furthermore, IFN-α produced by pDCs upon TLR-9 stimulation enhances both CD4+CXCR3+ T cells expansion and CXCR3 ligands production by endothelial cells in vitro. Eventually, TLR-9 stimulation of pDCs was shown to accelerate atherosclerosis development in ApoE-/- mice by enhancing the CD4+CXCR3+ T cells recruitment in arterial wall.

Conclusion: In SLE, IFN-α produced by pDCs both expands CD4+T cells expressing CXCR3 and induces endothelial cells to secrete CXCR3 ligands, which drive CD4+T cell migration into the arterial wall and atherosclerosis. Our findings support a multi-step model in which SLE-immune dysfunction is associated with the development of atherosclerosis

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/lupus-drives-atherosclerosis-through-cd4cxcr3-t-cells-and-plasmacytoid-dendritic-cells/