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Title 

Indoleamine 2,3-dioxygenase-expressing aortic plasmacytoid dendritic cells protect against atherosclerosis by induction of regulatory T cells

Authors 

T J YunJ S LeeK MachmachD ShimJ ChoiY J WiH S JangI H JungK KimWoon Kee YoonM A MiahB LiJ ChangM G BegoT N Q PhamJ LoschkoJ H FritzA B KrugS P LeeT KelerJ V GuimondE HaddadE A CohenM G SiroisI El-HamamsyM ColonnaG T OhJ H ChoiC Cheong

Publisher 

Elsevier (Cell Press)

Issue Date 

2016

Citation 

Cell Metabolism, vol. 23, no. 5, pp. 852-866

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.

ISSN 

1550-4131

Link 

http://dx.doi.org/10.1016/j.cmet.2016.04.010

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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