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)
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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 |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | McInnes, Professor Iain and Garside, Professor Paul and Brewer, Professor James and MacRitchie, Dr Neil and Maffia, Professor Pasquale and Gordon, Mr Peter and Grassia, Dr Gianluca 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 > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
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 |
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