Indoleamine 2,3-Dioxygenase-Expressing Aortic Plasmacytoid Dendritic Cells Protect against Atherosclerosis by Induction of Regulatory T Cells.
Cell Metab
; 23(5): 852-66, 2016 05 10.
Article
en En
| MEDLINE
| ID: mdl-27166946
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Aorta
/
Células Dendríticas
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Linfocitos T Reguladores
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Aterosclerosis
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Indolamina-Pirrol 2,3,-Dioxigenasa
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2016
Tipo del documento:
Article