MHC Class II-Restricted Antigen Presentation by Plasmacytoid Dendritic Cells Drives Pro-Atherogenic T Cell Immunity
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 BM transplanted into Ldlr-/- mice. Compared to 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 to controls without reductions in pDC numbers or changes in conventional DCs. MHCII-deficient pDCs showed defective stimulation of ApoB100-specific CD4+ T cells in response to native LDL, whereas production of IFN-α was not affected. Finally, the athero-protective effect of selective MHCII deficiency in pDCs was associated with significant reductions of pro-atherogenic T cell-derived Ifn-γ and lesional T cell infiltration, and was abrogated in CD4+ T cell-depleted animals.
Conclusions—This study supports a pro-atherogenic role for pDCs in murine atherosclerosis and identifies a critical role for MHCII-restricted antigen presentation by pDCs in driving pro-atherogenic T cell immunity.
- Plasmacytoid Dendritic cell
- T cell
- Interferon gamma
- immune system
- low-density lipoprotein
- Received May 9, 2014.
- Revision received July 9, 2014.
- Accepted August 4, 2014.