Plasmacytoid Dendritic Cells in Atherosclerosis

Abstract

Atherosclerosis, a chronic inflammatory disease of the vessel wall and the underlying cause of cardiovascular disease, is initiated and maintained by innate and adaptive immunity. Accumulating evidence suggests an important contribution of autoimmune responses to this disease. Plasmacytoid dendritic cells (pDCs), a specialized cell type known to produce large amounts of type I interferons (IFNs) in response to bacterial and viral infections, have recently been revealed to play important roles in atherosclerosis. For example, the development of autoimmune complexes consisting of self-DNA and antimicrobial peptides, which trigger chronic type I IFN production by pDCs, promote early atherosclerotic lesion formation. pDCs and pDC-derived type I IFNs can also induce the maturation of conventional DCs and macrophages, and the development of autoreactive B cells and antibody production. These mechanisms, known to play a role in the pathogenesis of other autoimmune diseases such as systemic lupus erythematosus and psoriasis, may also affect the development and progression of atherosclerotic lesion formation. This review discusses emerging evidence showing a contribution of pDCs in the onset and progression of atherosclerosis.

Molecular Biology of Atherosclerosis

“…These changes were accompanied by increased Th1 proliferation and production of associated cytokines, possibly due to the removal of indoleamine 2,3-dioxygenase (IDO), which is found in pDC and which was shown to inhibit CD4ϩ cell proliferation (376). Why opposite results were obtained remains puzzling but may be related to differences in the models, the antibody used to deplete the pDC, and possibly the stage of atherosclerosis (441). Possibly too, immune responses in ApoE versus LDLR null mice may have been markedly different.…”

“…Increased levels of type I interferons have been correlated with instability in human plaque (441). Repeated injections of IFN-␣ or IFN-␤ increased atherosclerosis in hyperlipidemic mice (see TABLE 7).…”

“…In vitro, IFN-␣ stimulates vigorous production of IFN-␥ and TRAIL (TNF-related apoptosis inducing ligand) by Th1 cells sufficient to kill VSMC. In addition, IFN-␣ amplifies innate immune responses by inducing upregulation of TLR4 on conventional DCs, as well as their production of TNF-␣, IL-12, and IL-23 (441).…”

Recent insights into the implications of metabolism in plasmacytoid dendritic cell innate functions: Potential ways to control these functions

“…Therefore, PDC have been reported to infiltrate acute graft- versus -host disease lesions, including gastro-intestinal 73 and cutaneous 74 lesions. PDC emerge as cells present in atherosclerotic plaques and may play a role in atherosclerosis 66, 75 . Atherosclerotic plaques are enriched in lipids.…”

The anti-inflammatory effects of platelet-derived microparticles in human plasmacytoid dendritic cells involve liver X receptor activation

“…Adam Ceroi, [1][2][3][4] Fanny Angelot Delettre, [1][2][3][4] Charline Marotel, [1][2][3] Thierry Gauthier, [1][2][3][4] Afag Asgarova, [1][2][3] Sabéha Biichlé, [1][2][3][4] Anne Duperrier, [1][2][3] Guillaume Mourey, [1][2][3] Sylvain Perruche, [1][2][3][4] Laurent Lagrost, [4][5][6][7] David Masson, [4][5][6][7] …”