title: Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin β Receptors.
abstract: Tertiary lymphoid organs (TLOs) emerge during nonresolving peripheral inflammation, but their impact on disease progression remains unknown. We have found in aged Apoe(-/-) mice that artery TLOs (ATLOs) controlled highly territorialized aorta T cell responses. ATLOs promoted T cell recruitment, primed CD4(+) T cells, generated CD4(+), CD8(+), T regulatory (Treg) effector and central memory cells, converted naive CD4(+) T cells into induced Treg cells, and presented antigen by an unusual set of dendritic cells and B cells. Meanwhile, vascular smooth muscle cell lymphotoxin β receptors (VSMC-LTβRs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LTβRs did not affect secondary lymphoid organs: Atherosclerosis was markedly exacerbated in Apoe(-/-)Ltbr(-/-) and to a similar extent in aged Apoe(-/-)Ltbr(fl/fl)Tagln-cre mice. These data support the conclusion that the immune system employs ATLOs to organize aorta T cell homeostasis during aging and that VSMC-LTβRs participate in atherosclerosis protection via ATLOs.
authors.affiliation: Institute of Molecular Immunology, Helmholtz Zentrum München, Marchioninistrasse 25, 81377 Munich, Germany; Leibniz Institute for Age Research, Fritz Lipmann-Institute, 07745 Jena, Germany.
authors.forename: Desheng
authors.initials: D
authors.lastname: Hu
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University, Pettenkoferstrasse 9, 80336 Munich, Germany.
authors.forename: Sarajo K
authors.initials: SK
authors.lastname: Mohanta
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University, Pettenkoferstrasse 9, 80336 Munich, Germany.
authors.forename: Changjun
authors.initials: C
authors.lastname: Yin
authors.affiliation: Leibniz Institute for Age Research, Fritz Lipmann-Institute, 07745 Jena, Germany; Department of Traditional Chinese Medicine, Medical College of Xiamen University, Xiamen University, 361102 Xiamen, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Peng
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University, Pettenkoferstrasse 9, 80336 Munich, Germany.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Leibniz Institute for Age Research, Fritz Lipmann-Institute, 07745 Jena, Germany; Cardiovascular Research Center (CVRC), University of Virginia, 415 Lane Rd, Post Box 801394, Charlottesville, VA 22908, USA.
authors.forename: Prasad
authors.initials: P
authors.lastname: Srikakulapu
authors.affiliation: Centre for Immunobiology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK; Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Grassia
authors.affiliation: Centre for Immunobiology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: MacRitchie
authors.affiliation: Centre for Immunobiology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
authors.forename: Gary
authors.initials: G
authors.lastname: Dever
authors.affiliation: Centre for Immunobiology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK; Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Gordon
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, G12 8TA, UK.
authors.forename: Francis L
authors.initials: FL
authors.lastname: Burton
authors.affiliation: Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Ialenti
authors.affiliation: Centre for Immunobiology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
authors.forename: Suleman R
authors.initials: SR
authors.lastname: Sabir
authors.affiliation: Centre for Immunobiology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.affiliation: Centre for Immunobiology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
authors.forename: James M
authors.initials: JM
authors.lastname: Brewer
authors.affiliation: Centre for Immunobiology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Garside
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University, Pettenkoferstrasse 9, 80336 Munich, Germany; DZHK, German Center for Cardiovascular Research, Munich Heart Alliance, Pettenkoferstrasse 9, 80336 Munich, Germany; and Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands.
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.affiliation: Institute for Medical Statistics, University of Jena, Jena University Hospital, 07743 Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehmann
authors.affiliation: Department for Laboratory Medicine, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Teupser
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University, Pettenkoferstrasse 9, 80336 Munich, Germany; II. Medizinische Klinik und Poliklinik; Technische Universität Muenchen, Klinikum rechts der Isar, Ismaningerstrasse 22, 81675 Munich, Germany.
authors.forename: Livia
authors.initials: L
authors.lastname: Habenicht
authors.affiliation: Department for Information Technology, University of Jena, Jena University Hospital, 07743 Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Beer
authors.affiliation: Leibniz Institute for Age Research, Fritz Lipmann-Institute, 07745 Jena, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Grabner
authors.affiliation: Centre for Immunobiology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK; Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Maffia
authors.affiliation: Leibniz Institute for Age Research, Fritz Lipmann-Institute, 07745 Jena, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Weih
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University, Pettenkoferstrasse 9, 80336 Munich, Germany. Electronic address: andreas.habenicht@med.uni-muenchen.de.
authors.forename: Andreas J R
authors.initials: AJ
authors.lastname: Habenicht
mesh_terms: D063194:Adventitia / Q000276:immunology; D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D002828:Choristoma / Q000276:immunology; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000235:genetics; D008221:Lymphoid Tissue / Q000276:immunology; D053259:Lymphotoxin beta Receptor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D001057:Apolipoproteins E; D053259:Lymphotoxin beta Receptor; D008840:Microfilament Proteins; D009124:Muscle Proteins; C051615:transgelin