title: Indoleamine 2,3-Dioxygenase-Expressing Aortic Plasmacytoid Dendritic Cells Protect against Atherosclerosis by Induction of Regulatory T Cells.
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.
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada; Division of Experimental Medicine, Department of Medicine, McGill University, Montréal, QC H3A 1A3, Canada.
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Yun
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada; Department of Microbiology, Infectiology, and Immunology, Université de Montréal, Montréal, QC H3C 3J7, Canada.
authors.forename: Jun Seong
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada; Department of Microbiology, Infectiology, and Immunology, Université de Montréal, Montréal, QC H3C 3J7, Canada.
authors.forename: Kawthar
authors.initials: K
authors.lastname: Machmach
authors.affiliation: Department of Life Science, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, South Korea.
authors.forename: Dahee
authors.initials: D
authors.lastname: Shim
authors.affiliation: Department of Life Science, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, South Korea.
authors.forename: Junhee
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Life Science, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, South Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Wi
authors.affiliation: Department of Life Science, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, South Korea.
authors.forename: Hyung Seok
authors.initials: HS
authors.lastname: Jang
authors.affiliation: Department of Life Sciences, Ewha Womans University, Seoul 120-750, South Korea.
authors.forename: In-Hyuk
authors.initials: IH
authors.lastname: Jung
authors.affiliation: Department of Life Science, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, South Korea.
authors.forename: Kyeongdae
authors.initials: K
authors.lastname: Kim
authors.affiliation: Laboratory Animal Resource Center, KRIBB, Chungbuk 363-883, South Korea.
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Yoon
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada; Department of Microbiology, Infectiology, and Immunology, Université de Montréal, Montréal, QC H3C 3J7, Canada.
authors.forename: Mohammad Alam
authors.initials: MA
authors.lastname: Miah
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada; Department of Molecular Biology, Université de Montréal, Montréal, QC H3C 3J7, Canada.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada; Department of Molecular Biology, Université de Montréal, Montréal, QC H3C 3J7, Canada.
authors.forename: Jinsam
authors.initials: J
authors.lastname: Chang
authors.affiliation: Laboratory of Human Retrovirology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada.
authors.forename: Mariana G
authors.initials: MG
authors.lastname: Bego
authors.affiliation: Laboratory of Human Retrovirology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada.
authors.forename: Tram N Q
authors.initials: TN
authors.lastname: Pham
authors.affiliation: Institute for Immunology, Ludwig-Maximilians-Universität München, München 80336, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Loschko
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montréal, QC H3A 2B4, Canada.
authors.forename: Jörg Hermann
authors.initials: JH
authors.lastname: Fritz
authors.affiliation: Institute for Immunology, Ludwig-Maximilians-Universität München, München 80336, Germany.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Krug
authors.affiliation: Cardiovascular Center, and Department of Internal Medicine, Seoul National University Hospital, Seoul 110-744, South Korea.
authors.forename: Seung-Pyo
authors.initials: SP
authors.lastname: Lee
authors.affiliation: Celldex Therapeutics, Hampton, NJ 08827, USA.
authors.forename: Tibor
authors.initials: T
authors.lastname: Keler
authors.affiliation: Centre de Santé et de Services Sociaux Jeanne-Mance, Montréal, QC H2H 2B4, Canada.
authors.forename: Jean V
authors.initials: JV
authors.lastname: Guimond
authors.affiliation: Department of Microbiology, Infectiology, and Immunology, Université de Montréal, Montréal, QC H3C 3J7, Canada; CHU Sainte-Justine Research Center, Montréal, QC H3T 1C5, Canada.
authors.forename: Elie
authors.initials: E
authors.lastname: Haddad
authors.affiliation: Department of Microbiology, Infectiology, and Immunology, Université de Montréal, Montréal, QC H3C 3J7, Canada; Laboratory of Human Retrovirology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Cohen
authors.affiliation: Research Center, Montréal Heart Institute, Montréal, QC H1T 1C8, Canada; Department of Pharmacology, Université de Montréal, Montréal, QC H3C 3J7, Canada.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Sirois
authors.affiliation: Department of Cardiac Surgery, Montréal Heart Institute, Montréal, QC H1T 1C8, Canada.
authors.forename: Ismail
authors.initials: I
authors.lastname: El-Hamamsy
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.affiliation: Department of Life Sciences, Ewha Womans University, Seoul 120-750, South Korea. Electronic address: gootaeg@ewha.ac.kr.
authors.forename: Goo Taeg
authors.initials: GT
authors.lastname: Oh
authors.affiliation: Department of Life Science, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, South Korea. Electronic address: jchoi75@hanyang.ac.kr.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada; Division of Experimental Medicine, Department of Medicine, McGill University, Montréal, QC H3A 1A3, Canada; Department of Microbiology, Infectiology, and Immunology, Université de Montréal, Montréal, QC H3C 3J7, Canada. Electronic address: cheolho.cheong@ircm.qc.ca.
authors.forename: Cheolho
authors.initials: C
authors.lastname: Cheong
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001011:Aorta / Q000473:pathology*; D050197:Atherosclerosis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001853:Bone Marrow / Q000473:pathology; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000201:enzymology*; D000939:Epitopes; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007370:Interferon Type I / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011973:Receptors, LDL / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism
chemical_list: D000906:Antibodies; D000939:Epitopes; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007370:Interferon Type I; D008565:Membrane Proteins; D011973:Receptors, LDL; D051217:Toll-Like Receptor 9; C084881:flt3 ligand protein; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3