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

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Title
Indoleamine 2,3-dioxygenase-expressing aortic plasmacytoid dendritic cells protect against atherosclerosis by induction of regulatory T cells
Author(s)
T J Yun; J S Lee; K Machmach; D Shim; J Choi; Y J Wi; H S Jang; I H Jung; K Kim; Woon Kee Yoon; M A Miah; B Li; J Chang; M G Bego; T N Q Pham; J Loschko; J H Fritz; A B Krug; S P Lee; T Keler; J V Guimond; E Haddad; E A Cohen; M G Sirois; I El-Hamamsy; M Colonna; G T Oh; J H Choi; C Cheong
Bibliographic Citation
Cell Metabolism, vol. 23, no. 5, pp. 852-866
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.
ISSN
1550-4131
Publisher
Elsevier-Cell Press
DOI
http://dx.doi.org/10.1016/j.cmet.2016.04.010
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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