Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-021-23909-z
Keywords
-
Categories
Funding
- Deutsche Forschungsgemeinschaft [CRC 1123, TRR259]
- Dutch Heart Foundation
- Dutch Federation of University Medical Centres
- Netherlands Organization for Health Research and Development
- Royal Netherlands Academy of Sciences
- Netherlands Organization for Scientific Research (NWO)
- EU (Horizon 2020, REPROGRAM)
- German Centre for Cardiovascular Research (DZHK)
- European Research Council
- Swedish Research Council
- Swedish Heart and Lung Foundation
- Swedish Society for Medical Research
- Swedish Heart and Lung Association
- Swedish Stroke Association
- Swedish Foundation for Strategic Research [IRC15-0067]
- The Knut and Alice Wallenberg foundation
- Medical Faculty at Lund University
- Region Skane
Ask authors/readers for more resources
The CD40L-CD40 signaling axis plays a role in atherosclerosis. This study investigates the cell-specific functions of the most relevant CD40L-expressing cell types. Deficiency of T cell-derived CD40L reduces and stabilizes plaques through impaired Th1 polarization, while platelet-derived CD40L ameliorates atherothrombosis.
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-gamma 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-gamma 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. Previous studies have shown that the CD40L-CD40 signaling axis plays a role in atherosclerosis. Here the authors investigate the cell-specific functions of the most relevant CD40L-expressing cell types in atherosclerosis. Deficiency of T cell-derived CD40L reduces and stabilizes plaques through impaired Th1 polarization while platelet-derived CD40L ameliorates atherothrombosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available