ArticleThe Journal of clinical investigation2019
Thioredoxin-1 confines T cell alloresponse and pathogenicity in graft-versus-host disease.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 41 citations in OpenAlex.
- A randomized controlled trial of conventional GVHD prophylaxis with or without teprenone for the prevention of severe acute GVHD.Annals of hematology · 2025Trial
- Mitochondrial DAMPs as a critical driver in the development of acute graft versus host disease and emerging mitochondria targeted therapeutic strategies.Frontiers in immunology · 2025Review
- Exploring the Role of Thioredoxin system in Cancer Immunotherapy.Journal of Cancer · 2025Article
- Targeting PRMT1 prevents acute and chronic graft-versus-host disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Donor T cell STAT3 deficiency enables tissue PD-L1-dependent prevention of graft-versus-host disease while preserving graft-versus-leukemia activity.The Journal of clinical investigation · 2023Article
- Role of Gut Microbiota and Oxidative Stress in the Progression of Transplant-Related Complications following Hematopoietic Stem Cell Transplantation.Oxidative medicine and cellular longevity · 2023Review
- NAC, NAC, Knockin' on Heaven's door: Interpreting the mechanism of action of N-acetylcysteine in tumor and immune cells.Redox biology · 2022Review
- Comprehensive ceRNA network for MACF1 regulates osteoblast proliferation.BMC genomics · 2022Article
- Redox regulation of the immune response.Cellular & molecular immunology · 2022Review
- Ceramide synthase 6 impacts T-cell allogeneic response and graft-versus-host disease through regulating N-RAS/ERK pathway.Leukemia · 2022Article
- Cascade of Inflammatory, Fibrotic Processes, and Stress-Induced Senescence in Chronic GVHD-Related Dry Eye Disease.International journal of molecular sciences · 2021Review
- Article
- Impact of Nrf2 expression in reconstituting T-cells of allogeneic hematopoietic stem cell transplanted patients.Leukemia · 2021Article
- Article
- T-Cell Metabolism in GraftFrontiers in immunology · 2021Review
- Recent Metabolic Advances for Preventing and Treating Acute and Chronic Graft Versus Host Disease.Frontiers in immunology · 2021Review
- Immunometabolism in haematopoietic stem cell transplantation and adoptive cellular therapies.Current opinion in hematology · 2020Review
- Distinct Regulatory and Effector T Cell Metabolic Demands during Graft-Versus-Host Disease.Trends in immunology · 2020Review
- Metabolic Pathways in Alloreactive T Cells.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Oxidative stress is elevated in the recipients of allogeneic hematopoietic transplantation (allo-HCT) and likely contributes to the development of graft-versus-host disease (GVHD). GVHD is characterized by activation, expansion, cytokine production and migration of alloreactive donor T cells, and remains a major cause of morbidity and mortality after allo-HCT. Hence, strategies to limit oxidative stress in GVHD are highly desirable. Thioredoxin1 (Trx1) counteracts oxidative stress by scavenging reactive oxygen species (ROS) and regulating other enzymes that metabolize H2O2. The present study sought to elucidate the role of Trx1 in the pathophysiology of GVHD. Using murine and xenograft models of allogeneic bone marrow transplantation (allo-BMT) and genetic (human Trx1-transgenic, Trx1-Tg) as well as pharmacologic (human recombinant Trx1, RTrx1) strategies; we found that Trx1-Tg donor T cells or administration of the recipients with RTrx1 significantly reduced GVHD severity. Mechanistically, we observed RTrx1 reduced ROS accumulation and cytokine production of mouse and human T cells in response to alloantigen stimulation in vitro. In allo-BMT settings, we found that Trx1-Tg or RTrx1 decreased downstream signaling molecules including NFκB activation and T-bet expression, and reduced proliferation, IFN-γ production and ROS accumulation in donor T cells within GVHD target organs. More importantly, administration of RTrx1 did not impair the graft-versus-leukemia (GVL) effect. Taken together, the current work provides a strong rationale and demonstrates feasibility to target the ROS pathway, which can be readily translated into clinic.
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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.