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

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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<sup>-/-</sup> mice that artery TLOs (ATLOs) controlled highly territorialized aorta Tcell responses. ATLOs promoted Tcell recruitment, primed CD4<sup>+</sup> Tcells, generated CD4<sup>+</sup>, CD8<sup>+</sup>, T regulatory (Treg) effector and central memory cells, converted naive CD4<sup>+</sup> Tcells into induced Treg cells, and presented antigen by an unusual set of dendritic cells and B cells. Meanwhile, vascular smooth muscle celllymphotoxin 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<sup>-/-</sup>Ltbr<sup>-/-</sup> and to a similar extent in aged Apoe<sup>-/-</sup>Ltbr<sup>fl/fl</sup>Tagln-cre mice. These data support the conclusion that the immune system employs ATLOs to organize aorta Tcell homeostasis during aging and that VSMC-LTβRs participate in atherosclerosis protection via ATLOs.

Original languageEnglish
Pages (from-to)1100-1115
Number of pages16
JournalImmunity
Volume42
Issue number6
DOIs
Publication statusPublished - 16 Jun 2015

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Keywords

  • atherosclerosis
  • vascular smooth muscle cells
  • Lymphotoxin β receptors

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