Abstract
Background: Triggering receptor expressed on myeloid cells (TREM)-1is identified as a major upstream proatherogenic receptor. However, the cellular processes modulated by TREM-1 in the development of atherosclerosis and plaque destabilization has not been fully elucidated. In this study, we investigated the effects of TREM-1 on dendritic cell maturation and dendritic cell–mediated T-cell activation induced by oxidized low-density lipoprotein (ox-LDL) in atherogenesis. Methods: Human peripheral blood monocytes were differentiated to dendritic cells and stimulated by ox-LDL. Naive autologous T cells were co-cultured with pretreated dendritic cells.The expressionof TREM-1 and the production of inflammatory cytokines were assessed by real-time PCR, western blot and ELISA.The expression of immune factors was determined with FACS to evaluate dendritic cell maturation and T-cell activation. Results: Stimulation with ox-LDL promoted dendritic cell maturation, TREM-1 expression and T-cell activation, and exposure of T cells to ox-LDL-treated dendritic cells induced production of interferon-γ and IL-17. Blocking TREM-1 suppressed dendritic cell maturation with low expression of CD1a, CD40, CD86 and HLA-DR, decreased production of TNF-α, IL-1β, IL-6 and MCP-1, and increased secretion of TGF-β and IL-10. In addition, stimulation of ox-LDL induced miR-155, miR-27, Let-7c and miR-185 expression, whereas inhibition of TREM-1 repressed miRNA-155. Silencing TREM-1 or miRNA-155 increased SOCS1 expression induced by ox-LDL. T cells derived from carotid atherosclerotic plaques or healthy individuals showed similar result patterns. Conclusion: These data suggest that TREM-1 modulates maturation of dendritic cells and activation of plaque T cells induced by ox-LDL, a pivotal player in atherogenesis.
Dendritic cell maturation by CD11c− T cells and Vα24+ natural killer T-cell activation by α-Galactosylceramide