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Indoleamine 2,3-Dioxygenase-Expressing Aortic Plasmacytoid Dendritic Cells Protect against Atherosclerosis by Induction of Regulatory T Cells

Title
Indoleamine 2,3-Dioxygenase-Expressing Aortic Plasmacytoid Dendritic Cells Protect against Atherosclerosis by Induction of Regulatory T Cells
Authors
Yun T.J.Lee J.S.Machmach K.Shim D.Choi J.Wi Y.J.Jang H.S.Jung I.-H.Kim K.Yoon W.K.Miah M.A.Li B.Chang J.Bego M.G.Pham T.N.Q.Loschko J.Fritz J.H.Krug A.B.Lee S.-P.Keler T.Guimond J.V.Haddad E.Cohen E.A.Sirois M.G.El-Hamamsy I.Colonna M.Oh G.T.Choi J.-H.Cheong C.
Ewha Authors
오구택
SCOPUS Author ID
오구택scopus
Issue Date
2016
Journal Title
Cell Metabolism
ISSN
1550-4131JCR Link
Citation
vol. 23, no. 5, pp. 852 - 866
Publisher
Cell Press
Indexed
SCI; SCIE; SCOPUS WOS scopus
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. © 2016 Elsevier Inc.
DOI
10.1016/j.cmet.2016.04.010
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자연과학대학 > 생명과학전공 > Journal papers
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