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Andreas Edsfeltdt

Andreas Edsfeldt

Associate professor

Andreas Edsfeltdt

Cell-specific and divergent roles of the CD40L-CD40 axis in atherosclerotic vascular disease

Author

  • Michael Lacy
  • Christina Bürger
  • Annelie Shami
  • Maiwand Ahmadsei
  • Holger Winkels
  • Katrin Nitz
  • Claudia M. van Tiel
  • Tom T.P. Seijkens
  • Pascal J.H. Kusters
  • Ela Karshovka
  • Koen H.M. Prange
  • Yuting Wu
  • Sanne L.N. Brouns
  • Sigrid Unterlugauer
  • Marijke J.E. Kuijpers
  • Myrthe E. Reiche
  • Sabine Steffens
  • Andreas Edsfeldt
  • Remco T.A. Megens
  • Johan W.M. Heemskerk
  • Isabel Goncalves
  • Christian Weber
  • Norbert Gerdes
  • Dorothee Atzler
  • Esther Lutgens

Summary, in English

Atherosclerosis is a major underlying cause of cardiovascular disease. Previous studies showed that inhibition of the co-stimulatory CD40 ligand (CD40L)-CD40 signaling axis profoundly attenuates atherosclerosis. As CD40L exerts multiple functions depending on the cell-cell interactions involved, we sought to investigate the function of the most relevant CD40L-expressing cell types in atherosclerosis: T cells and platelets. Atherosclerosis-prone mice with a CD40L-deficiency in CD4+ T cells display impaired Th1 polarization, as reflected by reduced interferon-γ production, and smaller atherosclerotic plaques containing fewer T-cells, smaller necrotic cores, an increased number of smooth muscle cells and thicker fibrous caps. Mice with a corresponding CD40-deficiency in CD11c+ dendritic cells phenocopy these findings, suggesting that the T cell-dendritic cell CD40L-CD40 axis is crucial in atherogenesis. Accordingly, sCD40L/sCD40 and interferon-γ concentrations in carotid plaques and plasma are positively correlated in patients with cerebrovascular disease. Platelet-specific deficiency of CD40L does not affect atherogenesis but ameliorates atherothrombosis. Our results establish divergent and cell-specific roles of CD40L-CD40 in atherosclerosis, which has implications for therapeutic strategies targeting this pathway.

Department/s

  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Cardiovascular Research - Translational Studies
  • EpiHealth: Epidemiology for Health

Publishing year

2021

Language

English

Publication/Series

Nature Communications

Volume

12

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Immunology in the medical area

Status

Published

Research group

  • Cardiovascular Research - Translational Studies

ISBN/ISSN/Other

  • ISSN: 2041-1723