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Indoleamine 2,3-Dioxygenase-Expressing Aortic Plasmacytoid Dendritic Cells Protect against Atherosclerosis by Induction of Regulatory T Cells.
- Source :
-
Cell metabolism [Cell Metab] 2016 May 10; Vol. 23 (5), pp. 852-66. - Publication Year :
- 2016
-
Abstract
- Plasmacytoid dendritic cells (pDCs) are unique bone-marrow-derived cells that produce large amounts of type I interferon in response to microbial stimulation. Furthermore, pDCs also promote T cell tolerance in sterile-inflammation conditions. However, the immunomodulatory role of aortic pDCs in atherosclerosis has been poorly understood. Here, we identified functional mouse and human pDCs in the aortic intima and showed that selective, inducible pDC depletion in mice exacerbates atherosclerosis. Aortic pDCs expressed CCR9 and indoleamine 2,3-dioxygenase 1 (IDO-1), an enzyme involved in driving the generation of regulatory T cells (Tregs). As a consequence, loss of pDCs resulted in decreased numbers of Tregs and reduced IL-10 levels in the aorta. Moreover, antigen presentation by pDCs expanded antigen-specific Tregs in the atherosclerotic aorta. Notably, Tregs ablation affected pDC homeostasis in diseased aorta. Accordingly, pDCs in human atherosclerotic aortas colocalized with Tregs. Collectively, we identified a mechanism of atheroprotection mediated by tolerogenic aortic pDCs.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antibodies pharmacology
Atherosclerosis immunology
Atherosclerosis pathology
Bone Marrow pathology
Cell Count
Cell Proliferation drug effects
Epitopes
Homeostasis drug effects
Humans
Interferon Type I metabolism
Macrophages drug effects
Macrophages metabolism
Membrane Proteins metabolism
Mice
Mice, Transgenic
Receptors, LDL metabolism
Time Factors
Toll-Like Receptor 9 metabolism
fms-Like Tyrosine Kinase 3 metabolism
Aorta pathology
Atherosclerosis enzymology
Atherosclerosis prevention & control
Dendritic Cells enzymology
Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-7420
- Volume :
- 23
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 27166946
- Full Text :
- https://doi.org/10.1016/j.cmet.2016.04.010