ArticleThe Journal of experimental medicine2010
Deficient CD40-TRAF6 signaling in leukocytes prevents atherosclerosis by skewing the immune response toward an antiinflammatory profile.
Article in The Journal of experimental medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 1 of them a synthesis that pooled it.
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Who cites it
132 citing papers in PubMed, 1 synthesis or guideline pooled it, 241 citations in OpenAlex.
- Integrative bioinformatics frameworks for abdominal aortic aneurysm using GWAS meta-analysis, biological network construction, and structural modeling.Scientific reports · 2025Pooled it
- Immune dysregulation and gut microbiota: Connection to health and disease development.Neural regeneration research · 2026Article
- Inflammation at the Crossroads: Familial Mediterranean Fever and Cardiovascular Risk.Mediterranean journal of rheumatology · 2026Article
- Human birth tissue products for pathological pain: mechanisms, evidence, and translational outlook.Journal of translational medicine · 2026Review
- CD40 drives tumor growth in non-small cell lung cancer via non-canonical immune-independent mechanisms.Cancer letters · 2026Article
- Identification of a PRDM1-regulated T cell network to regulate atherosclerotic plaque inflammation.Genome medicine · 2025Article
- CD40-TRAF6 inhibition suppresses cardiovascular inflammation, oxidative stress and functional complications in a mouse model of arterial hypertension.Redox biology · 2025Article
- Impact of statin therapy on CD40:CD40L signaling: mechanistic insights and therapeutic opportunities.Pharmacological reports : PR · 2025Review
- T cells in cardiac health and disease.The Journal of clinical investigation · 2025Review
- TNF superfamily molecules in atherosclerosis: mechanistic insights and therapeutic translation.Frontiers in immunology · 2025Review
- Non-rodent Models of Atherosclerosis: Repurposing of Existing Drugs and Search for Novel Treatment Strategies.Current cardiology reviews · 2025Review
- Structural bioinformatics for rational drug design.Research and practice in thrombosis and haemostasis · 2025Article
- Macrophage-based pathogenesis and theranostics of vulnerable plaques.Theranostics · 2025Review
- Role of inflammatory signaling pathways involving the CD40-CD40L-TRAF cascade in diabetes and hypertension-insights from animal and human studies.Basic research in cardiology · 2024Article
- Peritoneal Dialysis Aggravates and Accelerates Atherosclerosis in UremicJournal of the American Heart Association · 2024Article
- Targeting macrophages with multifunctional nanoparticles to detect and prevent atherosclerotic cardiovascular disease.Cardiovascular research · 2024Review
- Costimulatory and Coinhibitory Immune Checkpoints in Atherosclerosis: Therapeutic Targets in Atherosclerosis?JACC. Basic to translational science · 2024Review
- Significance of an altered lncRNA landscape in schizophrenia and cognition: clues from a case-control association study.European archives of psychiatry and clinical neuroscience · 2023Article
- Review
- Myeloid CD40 deficiency reduces atherosclerosis by impairing macrophages' transition into a pro-inflammatory state.Cardiovascular research · 2023Article
72 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 5 countries.
Funding
Abstract
The CD40-CD40 ligand (CD40L) signaling axis plays an important role in immunological pathways. Consequently, this dyad is involved in chronic inflammatory diseases, including atherosclerosis. Inhibition of CD40L in apolipoprotein E (Apoe)-deficient (Apoe(-/-)) mice not only reduced atherosclerosis but also conferred a clinically favorable plaque phenotype that was low in inflammation and high in fibrosis. Blockade of CD40L may not be therapeutically feasible, as long-term inhibition will compromise systemic immune responses. Conceivably, more targeted intervention strategies in CD40 signaling will have less deleterious side effects. We report that deficiency in hematopoietic CD40 reduces atherosclerosis and induces features of plaque stability. To elucidate the role of CD40-tumor necrosis factor receptor-associated factor (TRAF) signaling in atherosclerosis, we examined disease progression in mice deficient in CD40 and its associated signaling intermediates. Absence of CD40-TRAF6 but not CD40-TRAF2/3/5 signaling abolishes atherosclerosis and confers plaque fibrosis in Apoe(-/-) mice. Mice with defective CD40-TRAF6 signaling display a reduced blood count of Ly6C(high) monocytes, an impaired recruitment of Ly6C(+) monocytes to the arterial wall, and polarization of macrophages toward an antiinflammatory regulatory M2 signature. These data unveil a role for CD40-TRAF6, but not CD40-TRAF2/3/5, interactions in atherosclerosis and establish that targeting specific components of the CD40-CD40L pathway harbors the potential to achieve therapeutic effects in atherosclerosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.