{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:06:48Z","timestamp":1791158808245,"version":"4.1.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Objective\u2014<\/jats:italic>\n            <\/jats:bold>\n            Mouse aorta smooth muscle cells (SMC) express tumor necrosis factor receptor superfamily member 1A (TNFR-1) and lymphotoxin \u03b2-receptor (LT\u03b2R). Circumstantial evidence has linked the SMC LT\u03b2R to tertiary lymphoid organogenesis in hyperlipidemic mice. Here, we explored TNFR-1 and LT\u03b2R signaling in cultured SMC.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            TNFR-1 signaling activated the classical RelA NF-\u03baB pathway, whereas LT\u03b2R signaling activated the classical RelA and alternative RelB NF-\u03baB pathways, and both signaling pathways synergized to enhance p100 inhibitor processing to the p52 subunit of NF-\u03baB. Microarrays showed that simultaneous TNFR-1\/LT\u03b2R activation resulted in elevated mRNA encoding leukocyte homeostatic chemokines CCL2, CCL5, CXCL1, and CX3CL1. Importantly, SMC acquired features of lymphoid tissue organizers, which control tertiary lymphoid organogenesis in autoimmune diseases through hyperinduction of CCL7, CCL9, CXCL13, CCL19, CXCL16, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1. TNFR-1\/LT\u03b2R cross-talk resulted in augmented secretion of lymphorganogenic chemokine proteins. Supernatants of TNFR-1\/LT\u03b2R\u2013activated SMC markedly supported migration of splenic T cells, B cells, and macrophages\/dendritic cells. Experiments with\n            <jats:italic>ltbr<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            SMC indicated that LT\u03b2R-RelB activation was obligatory to generate the lymphoid tissue organizer phenotype.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusion\u2014<\/jats:italic>\n            <\/jats:bold>\n            SMC may participate in the formation of tertiary lymphoid tissue in atherosclerosis by upregulation of lymphorganogenic chemokines involved in T-lymphocyte, B-lymphocyte, and macrophage\/dendritic cell attraction.\n          <\/jats:p>","DOI":"10.1161\/atvbaha.109.191395","type":"journal-article","created":{"date-parts":[[2010,2,6]],"date-time":"2010-02-06T02:57:45Z","timestamp":1265425065000},"page":"395-402","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":96,"title":["Mouse Aorta Smooth Muscle Cells Differentiate Into Lymphoid Tissue Organizer-Like Cells on Combined Tumor Necrosis Factor Receptor-1\/Lymphotoxin \u03b2-Receptor NF-\u03baB Signaling"],"prefix":"10.1161","volume":"30","author":[{"given":"Katharina","family":"Lo\u0308tzer","sequence":"first","affiliation":[{"name":"From Institute for Vascular Medicine (K.L., S.D., S.C., R.G., R.S., B.L., M.B., M.H., A.J.R.H.), Friedrich Schiller University of Jena, Jena, Germany; Institute of Immunology (T.H.), University of Regensburg, Regensburg, Germany; Animal Research Institute (M.v.d.W.), Friedrich Schiller University of Jena, Jena, Germany; Department of Molecular Cell Biology and Immunology (R.E.M.), Vrje Universiteit Medical Center, Amsterdam, The Netherlands; Leibniz-Institute for Age Research\u2013Fritz-Lipmann-Institute..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Do\u0308pping","sequence":"additional","affiliation":[{"name":"From Institute for Vascular Medicine (K.L., S.D., S.C., R.G., R.S., B.L., M.B., M.H., A.J.R.H.), Friedrich Schiller University of Jena, Jena, Germany; Institute of Immunology (T.H.), University of Regensburg, Regensburg, Germany; Animal Research Institute (M.v.d.W.), Friedrich Schiller University of Jena, Jena, Germany; Department of Molecular Cell Biology and Immunology (R.E.M.), Vrje Universiteit Medical Center, Amsterdam, The Netherlands; Leibniz-Institute for Age Research\u2013Fritz-Lipmann-Institute..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Connert","sequence":"additional","affiliation":[{"name":"From Institute for Vascular Medicine (K.L., S.D., S.C., R.G., R.S., B.L., M.B., M.H., A.J.R.H.), Friedrich Schiller University of Jena, Jena, Germany; Institute of Immunology (T.H.), University of Regensburg, Regensburg, Germany; Animal Research Institute (M.v.d.W.), Friedrich Schiller University of Jena, Jena, Germany; Department of Molecular Cell Biology and Immunology (R.E.M.), Vrje Universiteit Medical Center, Amsterdam, The Netherlands; Leibniz-Institute for Age Research\u2013Fritz-Lipmann-Institute..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Gra\u0308bner","sequence":"additional","affiliation":[{"name":"From Institute for Vascular Medicine (K.L., S.D., S.C., R.G., R.S., B.L., M.B., M.H., A.J.R.H.), Friedrich Schiller University of Jena, Jena, Germany; Institute of Immunology (T.H.), University of Regensburg, Regensburg, Germany; Animal Research Institute (M.v.d.W.), Friedrich Schiller University of Jena, Jena, Germany; Department of Molecular Cell Biology and Immunology (R.E.M.), Vrje Universiteit Medical Center, Amsterdam, The Netherlands; Leibniz-Institute for Age Research\u2013Fritz-Lipmann-Institute..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Spanbroek","sequence":"additional","affiliation":[{"name":"From Institute for Vascular Medicine (K.L., S.D., S.C., R.G., R.S., B.L., M.B., M.H., A.J.R.H.), Friedrich Schiller University of Jena, Jena, Germany; Institute of Immunology (T.H.), University of Regensburg, Regensburg, Germany; Animal Research Institute (M.v.d.W.), Friedrich Schiller University of Jena, Jena, Germany; Department of Molecular Cell Biology and Immunology (R.E.M.), Vrje Universiteit Medical Center, Amsterdam, The Netherlands; Leibniz-Institute for Age Research\u2013Fritz-Lipmann-Institute..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Lemser","sequence":"additional","affiliation":[{"name":"From Institute for Vascular Medicine (K.L., S.D., S.C., R.G., R.S., B.L., M.B., M.H., A.J.R.H.), Friedrich Schiller University of Jena, Jena, Germany; Institute of Immunology (T.H.), University of Regensburg, Regensburg, Germany; Animal Research Institute (M.v.d.W.), Friedrich Schiller University of Jena, Jena, Germany; Department of Molecular Cell Biology and Immunology (R.E.M.), Vrje Universiteit Medical Center, Amsterdam, The Netherlands; Leibniz-Institute for Age Research\u2013Fritz-Lipmann-Institute..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Beer","sequence":"additional","affiliation":[{"name":"From Institute for Vascular Medicine (K.L., S.D., S.C., R.G., R.S., B.L., M.B., M.H., A.J.R.H.), Friedrich Schiller University of Jena, Jena, Germany; Institute of Immunology (T.H.), University of Regensburg, Regensburg, Germany; Animal Research Institute (M.v.d.W.), Friedrich Schiller University of Jena, Jena, Germany; Department of Molecular Cell Biology and Immunology (R.E.M.), Vrje Universiteit Medical Center, Amsterdam, The Netherlands; Leibniz-Institute for Age Research\u2013Fritz-Lipmann-Institute..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hildner","sequence":"additional","affiliation":[{"name":"From Institute for Vascular Medicine (K.L., S.D., S.C., R.G., R.S., B.L., M.B., M.H., A.J.R.H.), Friedrich Schiller University of Jena, Jena, Germany; Institute of Immunology (T.H.), University of Regensburg, Regensburg, Germany; Animal Research Institute (M.v.d.W.), Friedrich Schiller University of Jena, Jena, Germany; Department of Molecular Cell Biology and Immunology (R.E.M.), Vrje Universiteit Medical Center, Amsterdam, The Netherlands; Leibniz-Institute for Age Research\u2013Fritz-Lipmann-Institute..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hehlgans","sequence":"additional","affiliation":[{"name":"From Institute for Vascular Medicine (K.L., S.D., S.C., R.G., R.S., B.L., M.B., M.H., A.J.R.H.), Friedrich Schiller University of Jena, Jena, Germany; Institute of Immunology (T.H.), University of Regensburg, Regensburg, Germany; Animal Research Institute (M.v.d.W.), Friedrich Schiller University of Jena, Jena, Germany; Department of Molecular Cell Biology and Immunology (R.E.M.), Vrje Universiteit Medical Center, Amsterdam, The Netherlands; Leibniz-Institute for Age Research\u2013Fritz-Lipmann-Institute..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"van der Wall","sequence":"additional","affiliation":[{"name":"From Institute for Vascular Medicine (K.L., S.D., S.C., R.G., R.S., B.L., M.B., M.H., A.J.R.H.), Friedrich Schiller University of Jena, Jena, Germany; Institute of Immunology (T.H.), University of Regensburg, Regensburg, Germany; Animal Research Institute (M.v.d.W.), Friedrich Schiller University of Jena, Jena, Germany; Department of Molecular Cell Biology and Immunology (R.E.M.), Vrje Universiteit Medical Center, Amsterdam, The Netherlands; Leibniz-Institute for Age Research\u2013Fritz-Lipmann-Institute..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reina E.","family":"Mebius","sequence":"additional","affiliation":[{"name":"From Institute for Vascular Medicine (K.L., S.D., S.C., R.G., R.S., B.L., M.B., M.H., A.J.R.H.), Friedrich Schiller University of Jena, Jena, Germany; Institute of Immunology (T.H.), University of Regensburg, Regensburg, Germany; Animal Research Institute (M.v.d.W.), Friedrich Schiller University of Jena, Jena, Germany; Department of Molecular Cell Biology and Immunology (R.E.M.), Vrje Universiteit Medical Center, Amsterdam, The Netherlands; Leibniz-Institute for Age Research\u2013Fritz-Lipmann-Institute..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Lovas","sequence":"additional","affiliation":[{"name":"From Institute for Vascular Medicine (K.L., S.D., S.C., R.G., R.S., B.L., M.B., M.H., A.J.R.H.), Friedrich Schiller University of Jena, Jena, Germany; Institute of Immunology (T.H.), University of Regensburg, Regensburg, Germany; Animal Research Institute (M.v.d.W.), Friedrich Schiller University of Jena, Jena, Germany; Department of Molecular Cell Biology and Immunology (R.E.M.), Vrje Universiteit Medical Center, Amsterdam, The Netherlands; Leibniz-Institute for Age Research\u2013Fritz-Lipmann-Institute..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendalyn J.","family":"Randolph","sequence":"additional","affiliation":[{"name":"From Institute for Vascular Medicine (K.L., S.D., S.C., R.G., R.S., B.L., M.B., M.H., A.J.R.H.), Friedrich Schiller University of Jena, Jena, Germany; Institute of Immunology (T.H.), University of Regensburg, Regensburg, Germany; Animal Research Institute (M.v.d.W.), Friedrich Schiller University of Jena, Jena, Germany; Department of Molecular Cell Biology and Immunology (R.E.M.), Vrje Universiteit Medical Center, Amsterdam, The Netherlands; Leibniz-Institute for Age Research\u2013Fritz-Lipmann-Institute..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falk","family":"Weih","sequence":"additional","affiliation":[{"name":"From Institute for Vascular Medicine (K.L., S.D., S.C., R.G., R.S., B.L., M.B., M.H., A.J.R.H.), Friedrich Schiller University of Jena, Jena, Germany; Institute of Immunology (T.H.), University of Regensburg, Regensburg, Germany; Animal Research Institute (M.v.d.W.), Friedrich Schiller University of Jena, Jena, Germany; Department of Molecular Cell Biology and Immunology (R.E.M.), Vrje Universiteit Medical Center, Amsterdam, The Netherlands; Leibniz-Institute for Age Research\u2013Fritz-Lipmann-Institute..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas J.R.","family":"Habenicht","sequence":"additional","affiliation":[{"name":"From Institute for Vascular Medicine (K.L., S.D., S.C., R.G., R.S., B.L., M.B., M.H., A.J.R.H.), Friedrich Schiller University of Jena, Jena, Germany; Institute of Immunology (T.H.), University of Regensburg, Regensburg, Germany; Animal Research Institute (M.v.d.W.), Friedrich Schiller University of Jena, Jena, Germany; Department of Molecular Cell Biology and Immunology (R.E.M.), Vrje Universiteit Medical Center, Amsterdam, The Netherlands; Leibniz-Institute for Age 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