ArticleCell reports2024
Trained immunity is regulated by T cell-induced CD40-TRAF6 signaling.
Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed.
- Age-related differences in immune responses to inactivated influenza and adjuvanted recombinant herpes zoster vaccines.JCI insight · 2026Trial
- Innate Immune Memory Responses in Organ Transplantation.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Immune hyperactivity in hemodialysis patients is associated with interferon gamma-induced trained immunity.iScience · 2026Article
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- Trained immunity: new paradigm in the immunological memory of cardiovascular disease.ImmunoHorizons · 2026Review
- Mechanisms of Inflammation Chronification: Gene and Epigenetic Regulation of Intolerant Response (Trained Immunity).Current medicinal chemistry · 2026Article
- The recombinant zoster vaccine induces trained immunity in monocytes through persistent downregulation of TGFβ.PLoS pathogens · 2025Article
- Interferon gamma rebalances immunopathological signatures in chronic granulomatous disease through metabolic rewiring.Blood advances · 2025Article
- Trained Immunity in sepsis: Exploring the molecular link to long-term cardiometabolic disorders.Immunologic research · 2025Review
- The immune system in cardiovascular diseases: from basic mechanisms to therapeutic implications.Signal transduction and targeted therapy · 2025Review
- C1q reprograms innate immune memory.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
Trained immunity is characterized by histone modifications and metabolic changes in innate immune cells following exposure to inflammatory signals, leading to heightened responsiveness to secondary stimuli. Although our understanding of the molecular regulation of trained immunity has increased, the role of adaptive immune cells herein remains largely unknown. Here, we show that T cells modulate trained immunity via cluster of differentiation 40-tissue necrosis factor receptor-associated factor 6 (CD40-TRAF6) signaling. CD40-TRAF6 inhibition modulates functional, transcriptomic, and metabolic reprogramming and modifies histone 3 lysine 4 trimethylation associated with trained immunity. Besides in vitro studies, we reveal that single-nucleotide polymorphisms in the proximity of CD40 are linked to trained immunity responses in vivo and that combining CD40-TRAF6 inhibition with cytotoxic T lymphocyte antigen 4-immunoglobulin (CTLA4-Ig)-mediated co-stimulatory blockade induces long-term graft acceptance in a murine heart transplantation model. Combined, our results reveal that trained immunity is modulated by CD40-TRAF6 signaling between myeloid and adaptive immune cells and that this can be leveraged for therapeutic purposes.
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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 Socratic graph.