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

Desheng, Hu; Mohanta, S. a. r. a. j. o. &nbsp;. K.; Yin, Changjun; Peng, Li; Zhe, Ma; Srikakulapu, Prasad; Grassia, Gianluca; Macritchie, Neil; Dever, Gary; Gordon, Peter; Burton, F. r. a. n. c. i. s. &nbsp;. L.; Ialenti, Armando; Sabir, S. u. l. e. m. a. n. &nbsp;. R.; Mcinnes, I. a. i. n. &nbsp;. B.; Brewer, J. a. m. e. s. &nbsp;. M.; Garside, Paul; Weber, Christian; Lehmann, Thomas; Teupser, Daniel; Habenicht, Livia; Beer, Michael; Grabner, Rolf; Maffia, Pasquale; Weih, Falk; Habenicht, A. n. d. r. e. a. s. &nbsp;. J. R.

doi:10.1016/j.immuni.2015.05.015

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.

Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin β Receptors / Desheng, Hu; Mohanta, S. a. r. a. j. o.  . K.; Changjun, Yin; Li, Peng; Zhe, Ma; Prasad, Srikakulapu; Grassia, Gianluca; Neil, Macritchie; Gary, Dever; Peter, Gordon; Burton, F. r. a. n. c. i. s.  . L.; Ialenti, Armando; Sabir, S. u. l. e. m. a. n.  . R.; Mcinnes, I. a. i. n.  . B.; Brewer, J. a. m. e. s.  . M.; Paul, Garside; Christian, Weber; Thomas, Lehmann; Daniel, Teupser; Livia, Habenicht; Michael, Beer; Rolf, Grabner; Maffia, Pasquale; Falk, Weih; Habenicht, A. n. d. r. e. a. s.  . J. R.. - In: IMMUNITY. - ISSN 1074-7613. - 42:6(2015), pp. 1100-1115. [10.1016/j.immuni.2015.05.015]