title: CCL17-expressing dendritic cells drive atherosclerosis by restraining regulatory T cell homeostasis in mice.
abstract: Immune mechanisms are known to control the pathogenesis of atherosclerosis. However, the exact role of DCs, which are essential for priming of immune responses, remains elusive. We have shown here that the DC-derived chemokine CCL17 is present in advanced human and mouse atherosclerosis and that CCL17+ DCs accumulate in atherosclerotic lesions. In atherosclerosis-prone mice, Ccl17 deficiency entailed a reduction of atherosclerosis, which was dependent on Tregs. Expression of CCL17 by DCs limited the expansion of Tregs by restricting their maintenance and precipitated atherosclerosis in a mechanism conferred by T cells. Conversely, a blocking antibody specific for CCL17 expanded Tregs and reduced atheroprogression. Our data identify DC-derived CCL17 as a central regulator of Treg homeostasis, implicate DCs and their effector functions in atherogenesis, and suggest that CCL17 might be a target for vascular therapy.
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Svenja
authors.initials: S
authors.lastname: Meiler
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Döring
authors.forename: Miriam
authors.initials: M
authors.lastname: Koch
authors.forename: Maik
authors.initials: M
authors.lastname: Drechsler
authors.forename: Remco T A
authors.initials: RT
authors.lastname: Megens
authors.forename: Zuzanna
authors.initials: Z
authors.lastname: Rowinska
authors.forename: Kiril
authors.initials: K
authors.lastname: Bidzhekov
authors.forename: Caroline
authors.initials: C
authors.lastname: Fecher
authors.forename: Eliana
authors.initials: E
authors.lastname: Ribechini
authors.forename: Marc A M J
authors.initials: MA
authors.lastname: van Zandvoort
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Binder
authors.forename: Ivett
authors.initials: I
authors.lastname: Jelinek
authors.forename: Mihail
authors.initials: M
authors.lastname: Hristov
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.forename: Thomas
authors.initials: T
authors.lastname: Korn
authors.forename: Manfred B
authors.initials: MB
authors.lastname: Lutz
authors.forename: Irmgard
authors.initials: I
authors.lastname: Förster
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
authors.forename: Thomas
authors.initials: T
authors.lastname: Hieronymus
authors.forename: Tobias
authors.initials: T
authors.lastname: Junt
authors.forename: Alma
authors.initials: A
authors.lastname: Zernecke
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000276:immunology*; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D054414:Chemokine CCL17 / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D054414:Chemokine CCL17; D011993:Recombinant Fusion Proteins