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

Desheng Hu, Sarajo K. Mohanta, Changjun Yin, Li Peng, Zhe Ma, Prasad Srikakulapu, Gianluca Grassia, Neil MacRitchie, Gary Dever, Peter Gordon, Francis L. Burton, Armando Ialenti, Suleman R. Sabir, Iain B. McInnes, James M. Brewer, Paul Garside, Christian Weber, Thomas Lehmann, Daniel Teupser, Livia HabenichtMichael Beer, Rolf Grabner, Pasquale Maffia, Falk Weih, Andreas J. R. Habenicht*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Tertiary lymphoid organs (TLOs) emerge during non-resolving 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 beta receptors (VSMC-LT beta Rs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LT beta Rs 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-LT beta Rs participate in atherosclerosis protection via ATLOs.
Original languageEnglish
Pages (from-to)1100-1115
Issue number6
Publication statusPublished - 16 Jun 2015

Cite this