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

Hu, Desheng and Mohanta, Sarajo K. and Yin, Changjun and Peng, Li and Ma, Zhe and Srikakulapu, Prasad and Grassia, Gianluca and MacRitchie, Neil and Dever, Gary and Gordon, Peter and Burton, Francis L. and Ialenti, Armando and Sabir, Suleman R. and McInnes, Iain B. and Brewer, James M. and Garside, Paul and Weber, Christian and Lehmann, Thomas and Teupser, Daniel and Habenicht, Livia and Beer, Michael and Grabner, Rolf and Maffia, Pasquale and Weih, Falk and Habenicht, Andreas J R (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. ISSN 1097-4180 (https://doi.org/10.1016/j.immuni.2015.05.015)

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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.

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