title: Coinhibitory suppression of T cell activation by CD40 protects against obesity and adipose tissue inflammation in mice.
abstract: BACKGROUND
  Costimulatory cascades such as the CD40L-CD40 dyad enhance immune cell activation and inflammation during atherosclerosis. Here, we tested the hypothesis that CD40 directly modulates traits of the metabolic syndrome in diet-induced obesity in mice.
  
  
  RESULTS
  To induce the metabolic syndrome, wild-type or CD40(-/-) mice consumed a high-fat diet for 20 weeks. Unexpectedly, CD40(-/-) mice exhibited increased weight gain, impaired insulin secretion, augmented accumulation of inflammatory cells in adipose tissue, and enhanced proinflammatory gene expression. This proinflammatory and adverse metabolic phenotype could be transplanted into wild-type mice by reconstitution with CD40-deficient lymphocytes, indicating a major role for CD40 in T or B cells in this context. Conversely, therapeutic activation of CD40 signaling by the stimulating antibody FGK45 abolished further weight gain during the study, lowered glucose levels, improved insulin sensitivity, and suppressed adipose tissue inflammation. Mechanistically, CD40 activation decreased the expression of proinflammatory cytokines in T cells but not in B cells or macrophages. Finally, repopulation of lymphocyte-free Rag1(-/-) mice with CD40(-/-) T cells provoked dysmetabolism and inflammation, corroborating a protective role of CD40 on T cells in the metabolic syndrome. Finally, levels of soluble CD40 showed a positive association with obesity in humans, suggesting clinical relevance of our findings.
  
  
  CONCLUSIONS
  We present the surprising finding that CD40 deficiency on T cells aggravates whereas activation of CD40 signaling improves adipose tissue inflammation and its metabolic complications. Therefore, positive modulation of the CD40 pathway might describe a novel therapeutic concept against cardiometabolic disease.
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Dennis
authors.initials: D
authors.lastname: Wolf
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Felix
authors.initials: F
authors.lastname: Jehle
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Nathaly Anto
authors.initials: NA
authors.lastname: Michel
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Eva Nora
authors.initials: EN
authors.lastname: Bukosza
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rivera
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Yung Chih
authors.initials: YC
authors.lastname: Chen
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Natalie
authors.initials: N
authors.lastname: Hoppe
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Bianca
authors.initials: B
authors.lastname: Dufner
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Alexandra Ortiz
authors.initials: AO
authors.lastname: Rodriguez
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Christian
authors.initials: C
authors.lastname: Colberg
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Leandro
authors.initials: L
authors.lastname: Nieto
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rupprecht
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Ansgar
authors.initials: A
authors.lastname: Wiedemann
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Lisa
authors.initials: L
authors.lastname: Schulte
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Alexander
authors.initials: A
authors.lastname: Peikert
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Nicole
authors.initials: N
authors.lastname: Bassler
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Andrey
authors.initials: A
authors.lastname: Lozhkin
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Sonja Patricia
authors.initials: SP
authors.lastname: Hergeth
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Peter
authors.initials: P
authors.lastname: Stachon
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Ingo
authors.initials: I
authors.lastname: Hilgendorf
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Florian
authors.initials: F
authors.lastname: Willecke
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Constantin
authors.initials: C
authors.lastname: von Zur Mühlen
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Dominik
authors.initials: D
authors.lastname: von Elverfeldt
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Binder
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Peter
authors.initials: P
authors.lastname: Aichele
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Nerea
authors.initials: N
authors.lastname: Varo
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Mark A
authors.initials: MA
authors.lastname: Febbraio
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.). karlheinz.peter@bakeridi.edu.au.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
authors.affiliation: From the Atherogenesis Research Group, University Heart Center (D.W., F.J., N.A.M., E.N.B., N.H., B.D., A.O.R., C.C., L.N., B.R., A.W., L.S., A.P., A.L., S.P.H., P.S., I.H., F.W., C.v.z.M., C.B., A.Z.) and Institute for Medical Microbiology and Hygiene, Department of Immunology (P.A.), University of Freiburg, Freiburg, Germany; Atherothrombosis and Vascular Biology (F.J., J.R., Y.C.C., C.C., N.B., K.P.) and Cellular and Molecular Metabolism (M.A.F.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Freiburg, Germany (D.v.E.); Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria (C.J.B.); Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (N.V.); and Brigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Andreas
authors.initials: A
authors.lastname: Zirlik
mesh_terms: D017667:Adipocytes / Q000276:immunology / Q000378:metabolism; D000273:Adipose Tissue / Q000276:immunology*; D019264:Adoptive Transfer; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics* / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D023201:CD40 Ligand
keywords: CD40 ligand; adipose tissue; costimulatory and inhibitory T-cell receptors; inflammation; obesity