| Literature DB >> 27166946 |
Tae Jin Yun1, Jun Seong Lee2, Kawthar Machmach2, Dahee Shim3, Junhee Choi3, Young Jin Wi3, Hyung Seok Jang3, In-Hyuk Jung4, Kyeongdae Kim3, Won Kee Yoon5, Mohammad Alam Miah2, Bin Li6, Jinsam Chang6, Mariana G Bego7, Tram N Q Pham7, Jakob Loschko8, Jörg Hermann Fritz9, Anne B Krug8, Seung-Pyo Lee10, Tibor Keler11, Jean V Guimond12, Elie Haddad13, Eric A Cohen14, Martin G Sirois15, Ismail El-Hamamsy16, Marco Colonna17, Goo Taeg Oh18, Jae-Hoon Choi19, Cheolho Cheong20.
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.Entities:
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Year: 2016 PMID： 27166946 DOI： 10.1016/j.cmet.2016.04.010
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287