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Immunity. 2015 Jun 16;42(6):1100-15. doi: 10.1016/j.immuni.2015.05.015.

Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin β Receptors.

Author information

1
Institute of Molecular Immunology, Helmholtz Zentrum München, Marchioninistrasse 25, 81377 Munich, Germany; Leibniz Institute for Age Research, Fritz Lipmann-Institute, 07745 Jena, Germany.
2
Institute for Cardiovascular Prevention, Ludwig-Maximilians University, Pettenkoferstrasse 9, 80336 Munich, Germany.
3
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.
4
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.
5
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.
6
Centre for Immunobiology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
7
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.
8
Institute of Cardiovascular and Medical Sciences, University of Glasgow, G12 8TA, UK.
9
Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy.
10
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.
11
Institute for Medical Statistics, University of Jena, Jena University Hospital, 07743 Jena, Germany.
12
Department for Laboratory Medicine, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.
13
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.
14
Department for Information Technology, University of Jena, Jena University Hospital, 07743 Jena, Germany.
15
Leibniz Institute for Age Research, Fritz Lipmann-Institute, 07745 Jena, Germany.
16
Institute for Cardiovascular Prevention, Ludwig-Maximilians University, Pettenkoferstrasse 9, 80336 Munich, Germany. Electronic address: andreas.habenicht@med.uni-muenchen.de.

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.

PMID:
26084025
PMCID:
PMC4678289
DOI:
10.1016/j.immuni.2015.05.015
[Indexed for MEDLINE]
Free PMC Article

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