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Hu, D. ; Mohanta, S.K.* ; Yin, C.* ; Peng, L.* ; Ma, Z.* ; Srikakulapu, P.* ; Grassia, G.* ; MacRitchie, N.* ; Dever, G.* ; Gordon, P.M.* ; Burton, F.L.* ; Ialenti, A.* ; Sabir, S.R.* ; McInnes, I.B.* ; Brewer, J.M.* ; Garside, P.* ; Weber, C.* ; Lehmann, T.* ; Teupser, D.* ; Habenicht, L.* ; Beer, M.* ; Grabner, R.* ; Maffia, P.* ; Weih, F.* ; Habenicht, A.J.R.*

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

Immunity 42, 1100-1115 (2015)

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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.

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