1. MHC Class II-Restricted Antigen Presentation by Plasmacytoid Dendritic Cells Drives Proatherogenic T Cell Immunity.
- Author
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Sage, Andrew P., Murphy, Deirdre, Maffia, Pasquale, Masters, Leanne M., Sabir, Suleman R., Baker, Lauren L., Cambrook, Helen, Finigan, Alison J., Ait-Oufella, Hafid, Grassia, Gianluca, Harrison, James E., Ludewig, Burkhard, Reith, Walter, Hansson, Goran K., Reizis, Boris, Hugues, Stephanie, and Mallat, Ziad
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DENDRITIC cells , *ATHEROSCLEROSIS , *MAJOR histocompatibility complex , *IMMUNITY , *LYMPHOCYTES - Abstract
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-Cvc 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 apolipo-protein B 100-specific CD4+ T cells in response to native low-density lipoprotein, whereas production of interferon-α was not affected. Finally, the atheroprotective effect of selective MHCII deficiency in pDCs was associated with significant reductions of proatherogenic T cell-derived interferon-γ 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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