Artery tertiary lymphoid organs control aorta immunity and protect against atherosclerosis via vascular smooth muscle cell lymphotoxin β receptors

Hu, D. et al. (2015) Artery tertiary lymphoid organs control aorta immunity and protect against atherosclerosis via vascular smooth muscle cell lymphotoxin β receptors. Immunity, 42(6), pp. 1100-1115. (doi:10.1016/j.immuni.2015.05.015) (PMID:26084025) (PMCID:PMC4678289)

Hu, D. et al. (2015) Artery tertiary lymphoid organs control aorta immunity and protect against atherosclerosis via vascular smooth muscle cell lymphotoxin β receptors. Immunity, 42(6), pp. 1100-1115. (doi:10.1016/j.immuni.2015.05.015) (PMID:26084025) (PMCID:PMC4678289)

[img]
Preview
Text
107792.pdf - Published Version
Available under License Creative Commons Attribution.

9MB

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−/−Ltbrfl/flTagln-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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Maffia, Dr Pasquale and Gordon, Mr Peter and Garside, Professor Paul and Brewer, Professor James and Grassia, Dr Gianluca and MacRitchie, Mr Neil and Burton, Dr Francis and Dever, Dr Gary
Authors: Hu, D., Mohanta, S. K., Yin, C., Peng, L., Ma, Z., Srikakulapu, P., Grassia, G., MacRitchie, N., Dever, G., Gordon, P., Burton, F. L., Ialenti, A., Sabir, S. R., McInnes, I. B., Brewer, J. M., Garside, P., Weber, C., Lehmann, T., Teupser, D., Habenicht, L., Beer, M., Grabner, R., Maffia, P., Weih, F., and Habenicht, A. J.R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunity
Publisher:Cell Press
ISSN:1074-7613
ISSN (Online):1097-4180
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Immunity 42(6):100-1115
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
404921Investigating the role of T cells in vascular pathologyPaul GarsideBritish Heart Foundation (BHF)PG/06/083/21198III -IMMUNOLOGY
614711Defining innate and adaptive immune functions of plasmacytoid dendritic cells in atherosclerosis.Pasquale MaffiaBritish Heart Foundation (BHF)PG/12/81/29897III -IMMUNOLOGY