Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin beta 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 Habenicht; Michael Beer; Rolf Grabner; Pasquale Maffia; Falk Weih; Andreas J. R. Habenicht

doi:10.1016/j.immuni.2015.05.015

Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin beta 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Tertiary lymphoid organs (TLOs) emerge during non-resolving 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 beta receptors (VSMC-LT beta Rs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LT beta Rs 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-LT beta Rs participate in atherosclerosis protection via ATLOs.

Original language	English
Pages (from-to)	1100-1115
Journal	Immunity
Volume	42
Issue number	6
DOIs	https://doi.org/10.1016/j.immuni.2015.05.015
Publication status	Published - 16 Jun 2015

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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., Burton, F. L., Ialenti, A., Sabir, S. R., McInnes, I. B., Brewer, J. M., Garside, P., Weber, C., Lehmann, T., Teupser, D., ... Habenicht, A. J. R. (2015). Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin beta Receptors. Immunity, 42(6), 1100-1115. https://doi.org/10.1016/j.immuni.2015.05.015

@article{139a9e9562ee43ea9fe09c39c732baa7,

title = "Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin beta Receptors",

abstract = "Tertiary lymphoid organs (TLOs) emerge during non-resolving 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 beta receptors (VSMC-LT beta Rs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LT beta Rs 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-LT beta Rs participate in atherosclerosis protection via ATLOs.",

author = "Desheng Hu and Mohanta, {Sarajo K.} and Changjun Yin and Li Peng and Zhe Ma and Prasad Srikakulapu and Gianluca Grassia and Neil MacRitchie and Gary Dever and Peter Gordon and Burton, {Francis L.} and Armando Ialenti and Sabir, {Suleman R.} and McInnes, {Iain B.} and Brewer, {James M.} and Paul Garside and Christian Weber and Thomas Lehmann and Daniel Teupser and Livia Habenicht and Michael Beer and Rolf Grabner and Pasquale Maffia and Falk Weih and Habenicht, {Andreas J. R.}",

year = "2015",

month = jun,

day = "16",

doi = "10.1016/j.immuni.2015.05.015",

language = "English",

volume = "42",

pages = "1100--1115",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "6",

}

Hu, D, Mohanta, SK, Yin, C, Peng, L, Ma, Z, Srikakulapu, P, Grassia, G, MacRitchie, N, Dever, G, Gordon, P, Burton, FL, Ialenti, A, Sabir, SR, McInnes, IB, Brewer, JM, Garside, P, Weber, C, Lehmann, T, Teupser, D, Habenicht, L, Beer, M, Grabner, R, Maffia, P, Weih, F & Habenicht, AJR 2015, 'Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin beta Receptors', Immunity, vol. 42, no. 6, pp. 1100-1115. https://doi.org/10.1016/j.immuni.2015.05.015

TY - JOUR

T1 - Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin beta Receptors

AU - Hu, Desheng

AU - Mohanta, Sarajo K.

AU - Yin, Changjun

AU - Peng, Li

AU - Ma, Zhe

AU - Srikakulapu, Prasad

AU - Grassia, Gianluca

AU - MacRitchie, Neil

AU - Dever, Gary

AU - Gordon, Peter

AU - Burton, Francis L.

AU - Ialenti, Armando

AU - Sabir, Suleman R.

AU - McInnes, Iain B.

AU - Brewer, James M.

AU - Garside, Paul

AU - Weber, Christian

AU - Lehmann, Thomas

AU - Teupser, Daniel

AU - Habenicht, Livia

AU - Beer, Michael

AU - Grabner, Rolf

AU - Maffia, Pasquale

AU - Weih, Falk

AU - Habenicht, Andreas J. R.

PY - 2015/6/16

Y1 - 2015/6/16

N2 - Tertiary lymphoid organs (TLOs) emerge during non-resolving 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 beta receptors (VSMC-LT beta Rs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LT beta Rs 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-LT beta Rs participate in atherosclerosis protection via ATLOs.

AB - Tertiary lymphoid organs (TLOs) emerge during non-resolving 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 beta receptors (VSMC-LT beta Rs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LT beta Rs 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-LT beta Rs participate in atherosclerosis protection via ATLOs.

U2 - 10.1016/j.immuni.2015.05.015

DO - 10.1016/j.immuni.2015.05.015

M3 - Article

C2 - 26084025

SN - 1074-7613

VL - 42

SP - 1100

EP - 1115

JO - Immunity

JF - Immunity

IS - 6

ER -

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

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