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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adventitia / immunology
  • Aging / genetics
  • Aging / immunology*
  • Animals
  • Aorta / pathology
  • Apolipoproteins E / genetics
  • Atherosclerosis / genetics
  • Atherosclerosis / immunology*
  • Cell Differentiation / genetics
  • Cell Movement / genetics
  • Cells, Cultured
  • Choristoma / immunology
  • Immunologic Memory
  • Lymphocyte Activation / genetics
  • Lymphoid Tissue / immunology
  • Lymphotoxin beta Receptor / genetics
  • Lymphotoxin beta Receptor / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microfilament Proteins / genetics
  • Muscle Proteins / genetics
  • Myocytes, Smooth Muscle / physiology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*


  • Apolipoproteins E
  • Lymphotoxin beta Receptor
  • Microfilament Proteins
  • Muscle Proteins
  • transgelin

Associated data

  • GEO/GSE40156