MHC Class II-Restricted Antigen Presentation by Plasmacytoid Dendritic Cells Drives Proatherogenic T Cell Immunity

Article

关键词: LOW-DENSITY-LIPOPROTEIN;    CORONARY-ARTERY-DISEASE;    SMOOTH-MUSCLE CELLS;    IN-VIVO;    AGGRAVATES ATHEROSCLEROSIS;    REDUCES ATHEROSCLEROSIS;    CHRONIC INFLAMMATION;    VIRAL-INFECTION;    AORTIC INTIMA;    MICE;   

DOI  :  10.1161/CIRCULATIONAHA.114.011090

来源: SCIE

【 摘 要 】

Background-Plasmacytoid dendritic cells (pDCs) bridge innate and adaptive immune responses and are important regulators of immuno-inflammatory diseases. However, their role in atherosclerosis remains elusive. Methods and Results-Here, we used genetic approaches to investigate the role of pDCs in atherosclerosis. Selective pDC deficiency in vivo was achieved using CD11c-Cre x Tcf4(-/flox) bone marrow transplanted into Ldlr(-/-) mice. Compared with control Ldlr(-/-) chimeric mice, CD11c-Cre x Tcf4(-/flox) mice had reduced atherosclerosis levels. To begin to understand the mechanisms by which pDCs regulate atherosclerosis, we studied chimeric Ldlr(-/-) mice with selective MHCII deficiency on pDCs. Significantly, these mice also developed reduced atherosclerosis compared with controls without reductions in pDC numbers or changes in conventional DCs. MHCII-deficient pDCs showed defective stimulation of apolipoprotein B100-specific CD4(+) T cells in response to native low-density lipoprotein, whereas production of interferon-a was not affected. Finally, the atheroprotective effect of selective MHCII deficiency in pDCs was associated with significant reductions of proatherogenic T cell-derived interferon-gamma and lesional T cell infiltration, and was abrogated in CD4(+) T cell-depleted animals. Conclusions-This study supports a proatherogenic role for pDCs in murine atherosclerosis and identifies a critical role for MHCII-restricted antigen presentation by pDCs in driving proatherogenic T cell immunity.

【 授权许可】

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