TREM-1 modulates dendritic cell maturation and dendritic cell–mediated T cell activation induced by ox-LDL [post]

2020 unpublished
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
more » ... ipheral 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. Background Atherosclerosis is characterized by lipid accumulation and chronic inflammation of the arterial wall, involving both innate and adaptive immune responses. Dendritic cellshave been found within atherosclerotic lesions, and serve a key player in atherogenesis via antigen presentation, lipidsinternalization, and secretion of inflammatory cytokines [1] [2] [3] . These cells also have compact adhesion to endothelium, causingplaque rupture and thrombosis, and finally resulting in acute Not applicable.
doi:10.21203/rs.3.rs-17606/v1 fatcat:6jiz53tfmjav3pwbdxmmlcasyi