title: Artery tertiary lymphoid organs contribute to innate and adaptive immune responses in advanced mouse atherosclerosis.
abstract: Tertiary lymphoid organs emerge in tissues in response to nonresolving inflammation. Recent research characterized artery tertiary lymphoid organs in the aorta adventitia of aged apolipoprotein E-deficient mice. The atherosclerosis-associated lymphocyte aggregates are organized into distinct compartments, including separate T-cell areas harboring conventional, monocyte-derived, lymphoid, and plasmacytoid dendritic cells, as well as activated T-cell effectors and memory cells; B-cell follicles containing follicular dendritic cells in activated germinal centers; and peripheral niches of plasma cells. Artery tertiary lymphoid organs show marked neoangiogenesis, aberrant lymphangiogenesis, and extensive induction of high endothelial venules. Moreover, newly formed lymph node-like conduits connect the external lamina with high endothelial venules in T-cell areas and also extend into germinal centers. Mouse artery tertiary lymphoid organs recruit large numbers of naïve T cells and harbor lymphocyte subsets with opposing activities, including CD4(+) and CD8(+) effector and memory T cells, natural and induced CD4(+) regulatory T cells, and memory B cells at different stages of differentiation. These data suggest that artery tertiary lymphoid organs participate in primary immune responses and organize T- and B-cell autoimmune responses in advanced atherosclerosis. In this review, we discuss the novel concept that pro- and antiatherogenic immune responses toward unknown arterial wall-derived autoantigens may be organized by artery tertiary lymphoid organs and that disruption of the balance between pro- and antiatherogenic immune cell subsets may trigger clinically overt atherosclerosis.
authors.affiliation: From the Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany (S.K.M., C.Y., C.W., N.G., A.J.R.H.); Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena, Germany (L.P., P.S., V.B., F.W.); and Institute of Molecular Immunology, Helmholtz Center Munich, Neuherberg, Germany (D.H.).
authors.forename: Sarajo Kumar
authors.initials: SK
authors.lastname: Mohanta
authors.affiliation: From the Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany (S.K.M., C.Y., C.W., N.G., A.J.R.H.); Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena, Germany (L.P., P.S., V.B., F.W.); and Institute of Molecular Immunology, Helmholtz Center Munich, Neuherberg, Germany (D.H.).
authors.forename: Changjun
authors.initials: C
authors.lastname: Yin
authors.affiliation: From the Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany (S.K.M., C.Y., C.W., N.G., A.J.R.H.); Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena, Germany (L.P., P.S., V.B., F.W.); and Institute of Molecular Immunology, Helmholtz Center Munich, Neuherberg, Germany (D.H.).
authors.forename: Li
authors.initials: L
authors.lastname: Peng
authors.affiliation: From the Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany (S.K.M., C.Y., C.W., N.G., A.J.R.H.); Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena, Germany (L.P., P.S., V.B., F.W.); and Institute of Molecular Immunology, Helmholtz Center Munich, Neuherberg, Germany (D.H.).
authors.forename: Prasad
authors.initials: P
authors.lastname: Srikakulapu
authors.affiliation: From the Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany (S.K.M., C.Y., C.W., N.G., A.J.R.H.); Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena, Germany (L.P., P.S., V.B., F.W.); and Institute of Molecular Immunology, Helmholtz Center Munich, Neuherberg, Germany (D.H.).
authors.forename: Vineela
authors.initials: V
authors.lastname: Bontha
authors.affiliation: From the Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany (S.K.M., C.Y., C.W., N.G., A.J.R.H.); Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena, Germany (L.P., P.S., V.B., F.W.); and Institute of Molecular Immunology, Helmholtz Center Munich, Neuherberg, Germany (D.H.).
authors.forename: Desheng
authors.initials: D
authors.lastname: Hu
authors.affiliation: From the Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany (S.K.M., C.Y., C.W., N.G., A.J.R.H.); Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena, Germany (L.P., P.S., V.B., F.W.); and Institute of Molecular Immunology, Helmholtz Center Munich, Neuherberg, Germany (D.H.).
authors.forename: Falk
authors.initials: F
authors.lastname: Weih
authors.affiliation: From the Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany (S.K.M., C.Y., C.W., N.G., A.J.R.H.); Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena, Germany (L.P., P.S., V.B., F.W.); and Institute of Molecular Immunology, Helmholtz Center Munich, Neuherberg, Germany (D.H.).
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.affiliation: From the Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany (S.K.M., C.Y., C.W., N.G., A.J.R.H.); Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena, Germany (L.P., P.S., V.B., F.W.); and Institute of Molecular Immunology, Helmholtz Center Munich, Neuherberg, Germany (D.H.).
authors.forename: Norbert
authors.initials: N
authors.lastname: Gerdes
authors.affiliation: From the Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany (S.K.M., C.Y., C.W., N.G., A.J.R.H.); Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena, Germany (L.P., P.S., V.B., F.W.); and Institute of Molecular Immunology, Helmholtz Center Munich, Neuherberg, Germany (D.H.). Andreas.Habenicht@med.uni-muenchen.de.
authors.forename: Andreas J R
authors.initials: AJ
authors.lastname: Habenicht
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology*; D063194:Adventitia / Q000503:physiopathology*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D001158:Arteries / Q000503:physiopathology*; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D015551:Autoimmunity / Q000276:immunology / Q000502:physiology; D001402:B-Lymphocytes / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D008221:Lymphoid Tissue / Q000503:physiopathology*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: D001057:Apolipoproteins E
keywords: adventitia; aging; atherosclerosis; autoimmune response