Abstract
SummaryTertiary 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.
Highlights
We have found in aged ApoeÀ/À mice that artery Tertiary lymphoid organs (TLOs) (ATLOs) controlled highly territorialized aorta T cell responses
Vascular smooth muscle cell lymphotoxin b receptors (VSMC-LTbRs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though vascular smooth muscle cells (VSMCs)-LTbRs did not affect secondary lymphoid organs: Atherosclerosis was markedly exacerbated in ApoeÀ/ÀLtbrÀ/À and to a similar extent in aged ApoeÀ/ÀLtbrfl/flTagln-cre mice
ATLOs to organize aorta T cell homeostasis during aging and that VSMC-LTbRs participate in atherosclerosis protection via ATLOs
Summary
Changjun Yin, ..., Pasquale Maffia, Falk Weih, Andreas J.R. Habenicht. Tertiary lymphoid organs emerge during nonresolving inflammation. Habenicht and colleagues find that atherosclerosis immune responses are controlled by artery tertiary lymphoid organs in the adventitial connective tissue adjoining arteries. These lymphocyte aggregates arise through vascular smooth muscle cell lymphotoxin b receptor signaling and act as powerhouses of protective atherosclerosis immunity. Highlights d Artery tertiary lymphoid organs control atherosclerosis T cell immunity.
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