ArticleBlood2014
α-1-Antitrypsin (AAT)-modified donor cells suppress GVHD but enhance the GVL effect: a role for mitochondrial bioenergetics.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
- αBlood · 2018Trial
- Alpha 1 Antitrypsin Suppresses Autoantibody Production and Cellular Autoimmunity in Chronic Graft-Versus-Host Disease (cGVHD) in a Lupus Mouse Model.Biomolecules · 2026Article
- [Advances in the prevention and treatment of acute graft-versus-host disease with cellular and novel targeted immunotherapy].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Review
- SERPINA1 gene regulates the tumorigenesis and progression of breast cancer through PI3K/AKT signaling pathway and tumor immune microenvironment.Scientific reports · 2025Article
- Altered Serum Alpha1-Antitrypsin Protease Inhibition before and after Clinical Hematopoietic Stem Cell Transplantation: Association with Risk for Non-Relapse Mortality.International journal of molecular sciences · 2023Article
- Serpin Family A Member 1 Is Prognostic and Involved in Immunological Regulation in Human Cancers.International journal of molecular sciences · 2023Article
- Graft-versus-host disease: teaching old drugs new tricks at less cost.Frontiers in immunology · 2023Review
- Immune Suppression in Allogeneic Hematopoietic Stem Cell Transplantation.Handbook of experimental pharmacology · 2022Article
- α1-Antitrypsin attenuates acute rejection of orthotopic murine lung allografts.Respiratory research · 2021Article
- Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation.Scientific reports · 2021Article
- Boosted Pro-Inflammatory Activity in Human PBMCs by Lipopolysaccharide and SARS-CoV-2 Spike Protein Is Regulated by α-1 Antitrypsin.International journal of molecular sciences · 2021Article
- Profiling Tryptophan Catabolites of Human Gut Microbiota and Acute-Phase Protein Levels in Neonatal Dried Blood Specimens.Frontiers in microbiology · 2021Article
- The Pathophysiology and Treatment of Graft-Frontiers in immunology · 2021Review
- Renoprotective Effects of Alpha-1 Antitrypsin against Tacrolimus-Induced Renal Injury.International journal of molecular sciences · 2020Article
- Immunopathology and biology-based treatment of steroid-refractory graft-versus-host disease.Blood · 2020Review
- Targeting Signal 3 Extracellularly and Intracellularly in Graft-Versus-Host Disease.Frontiers in immunology · 2020Review
- Alpha-1-Antitrypsin Ameliorates Pristane Induced Diffuse Alveolar Hemorrhage in Mice.Journal of clinical medicine · 2019Article
- A patenting perspective on human neutrophil elastase (HNE) inhibitors (2014-2018) and their therapeutic applications.Expert opinion on therapeutic patents · 2019Review
- Alpha-1 Antitrypsin Attenuates Acute Lung Allograft Injury in a Rat Lung Transplant Model.Transplantation direct · 2019Article
- Clathrin-mediated Endocytosis of Alpha-1 Antitrypsin is Essential for its Protective Function in Islet Cell Survival.Theranostics · 2019Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Hematopoietic cell transplantation is curative in many patients. However, graft-versus-host disease (GVHD), triggered by alloreactive donor cells, has remained a major complication. Here, we show an inverse correlation between plasma α-1-antitrypsin (AAT) levels in human donors and the development of acute GVHD in the recipients (n = 111; P = .0006). In murine models, treatment of transplant donors with human AAT resulted in an increase in interleukin-10 messenger RNA and CD8(+)CD11c(+)CD205(+) major histocompatibility complex class II(+) dendritic cells (DCs), and the prevention or attenuation of acute GVHD in the recipients. Ablation of DCs (in AAT-treated CD11c-DTR donors) decreased CD4(+)CD25(+)FoxP3(+) regulatory T cells to one-third and abrogated the anti-GVHD effect. The graft-versus-leukemia (GVL) effect of donor cells (against A20 tumor cells) was maintained or even enhanced with AAT treatment of the donor, mediated by an expanded population of NK1.1(+), CD49B(+), CD122(+), CD335(+) NKG2D-expressing natural killer (NK) cells. Blockade of NKG2D significantly suppressed the GVL effect. Metabolic analysis showed a high glycolysis-high oxidative phosphorylation profile for NK1.1(+) cells, CD4(+)CD25(+)FoxP3(+) T cells, and CD11c(+) DCs but not for effector T cells, suggesting a cell type-specific effect of AAT. Thus, via altered metabolism, AAT exerts effective GVHD protection while enhancing GVL effects.
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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.