ArticleJCI insight2018
Complement C3a and C5a receptors promote GVHD by suppressing mitophagy in recipient dendritic cells.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
22 citing papers in PubMed, 37 citations in OpenAlex.
- A prospective phase 2 clinical trial of a C5a complement inhibitor for acute GVHD with lower GI tract involvement.Bone marrow transplantation · 2023Trial
- Autophagy in the Pathogenesis of Membranous Nephropathy.Kidney medicine · 2025Review
- Role of autophagy in rejection after solid organ transplantation: A systematic review of the literature.World journal of transplantation · 2025Review
- Cardiac Repair after Myocardial Infarction is Controlled by a Complement C5a Receptor 1-Driven Signaling Cascade.Thrombosis and haemostasis · 2025Article
- Efficacy of biomarkers and imaging techniques for the diagnosis of traumatic brain injury: challenges and opportunities.Molecular and cellular biochemistry · 2025Review
- Dual role of complement in neuronal repair.Frontiers in immunology · 2025Review
- p39 Affects Myelin Formation in Cerebral Ischemic Injury.Neuromolecular medicine · 2024Article
- Sphingolipid Signaling and Complement Activation in Glioblastoma: A Promising Avenue for Therapeutic Intervention.BioChem · 2024Article
- Autophagy differentially regulates tissue tolerance of distinct target organs in graft-versus-host disease models.The Journal of clinical investigation · 2024Article
- The Relationship between Complements and Age-Related Macular Degeneration and Its Pathogenesis.Journal of ophthalmology · 2024Review
- Mild Hypothermia Alleviates Complement C5a-Induced Neuronal Autophagy During Brain Ischemia-Reperfusion Injury After Cardiac Arrest.Cellular and molecular neurobiology · 2023Article
- Pentraxin 3 Inhibits Complement-driven Macrophage Activation to Restrain Granuloma Formation in Sarcoidosis.American journal of respiratory and critical care medicine · 2022Article
- Mannan-Binding Lectin Promotes Murine Graft-versus-Host Disease by Amplifying Lipopolysaccharide-Initiated Inflammation.Transplantation and cellular therapy · 2022Article
- Review
- The Role of Ceramide Metabolism and Signaling in the Regulation of Mitophagy and Cancer Therapy.Cancers · 2021Review
- Grape seed proanthocyanidins attenuate apoptosis in ischemic stroke.Acta neurologica Belgica · 2021Article
- More than a Pore: Nonlytic Antimicrobial Functions of Complement and Bacterial Strategies for Evasion.Microbiology and molecular biology reviews : MMBR · 2021Review
- Lysosomal Acid Lipase Is Required for Donor T Cells to Induce Graft-versus-Host Disease.Cell reports · 2020Article
- Targeting the Complement Alternative Pathway Permits Graft Versus Leukemia Activity while Preventing Graft Versus Host Disease.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Bone Marrow Transplantation Platform to Investigate the Role of Dendritic Cells in Graft-versus-Host Disease.Journal of visualized experiments : JoVE · 2020Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 4 countries.
Funding
Abstract
Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic cell transplantation (HCT). DCs play critical roles in GVHD induction. Modulating autophagy represents a promising therapeutic strategy for the treatment of immunological diseases. Complement receptors C3aR/C5aR expressed on DCs regulate immune responses by translating extracellular signals into intracellular activity. In the current study, we found that C3aR/C5aR deficiency enhanced ceramide-dependent lethal mitophagy (CDLM) in DCs. Cotransfer of host-type C3aR-/-/C5aR-/- DCs in the recipients significantly improved GVHD outcome after allogeneic HCT, primarily through enhancing CDLM in DCs. C3aR/C5aR deficiency in the host hematopoietic compartment significantly reduced GVHD severity via impairing Th1 differentiation and donor T cell glycolytic activity while enhancing Treg generation. Prophylactic treatment with C3aR/C5aR antagonists effectively alleviated GVHD while maintaining the graft-versus-leukemia (GVL) effect. Altogether, we demonstrate that inhibiting C3aR/C5aR induces lethal mitophagy in DCs, which represents a potential therapeutic approach to control GVHD while preserving the GVL effect.
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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.