ArticleJCI insight2020
PRMT5 regulates T cell interferon response and is a target for acute graft-versus-host disease.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 37 citations in OpenAlex.
- Enhancing CD8Biomolecules · 2025Article
- DNMT1 silencing induces KIR2DL1/2/3 expression via methylation to alleviate graft-Histology and histopathology · 2025Article
- PRMT5 inhibition reduces hyperinflammation in a murine model of secondary hemophagocytic lymphohistiocytosis.Blood advances · 2025Article
- PRMT5: splicing up tolerance.The Journal of clinical investigation · 2024Article
- Identification and validation of anti-protein arginine methyltransferase 5 (PRMT5) antibody as a novel biomarker for systemic sclerosis (SSc).Annals of the rheumatic diseases · 2024Article
- A PRMT5-ZNF326 axis mediates innate immune activation upon replication stress.Science advances · 2024Article
- The Role of Protein Methyltransferases in Immunity.Molecules (Basel, Switzerland) · 2024Review
- Review
- Inhibiting post-translational methylation to prevent GVHD.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Targeting PRMT1 prevents acute and chronic graft-versus-host disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Article
- Review
- PRMT5 regulates epigenetic changes in suppressive Th1-like iTregs in response to IL-12 treatment.Frontiers in immunology · 2023Article
- Protein arginine methylation in viral infection and antiviral immunity.International journal of biological sciences · 2023Review
- PRMT5 in T Cells Drives Th17 Responses, Mixed Granulocytic Inflammation, and Severe Allergic Airway Inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- The Influence of Arginine Methylation in Immunity and Inflammation.Journal of inflammation research · 2022Review
- Protein Arginine Methylation: An Emerging Modification in Cancer Immunity and Immunotherapy.Frontiers in immunology · 2022Review
- Cancer synthetic vulnerabilities to protein arginine methyltransferase inhibitors.Current opinion in pharmacology · 2021Review
- Protein arginine methylation: from enigmatic functions to therapeutic targeting.Nature reviews. Drug discovery · 2021Review
- Post-Translational Modifications in Transcription Factors that Determine T Helper Cell Differentiation.Molecules and cells · 2021Review
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
Abstract
Acute graft-versus-host disease (aGVHD) is a T cell-mediated immunological disorder and the leading cause of nonrelapse mortality in patients who receive allogeneic hematopoietic cell transplants. Based on recent observations that protein arginine methyltransferase 5 (PRMT5) and arginine methylation are upregulated in activated memory T cells, we hypothesized that PRMT5 is involved in the pathogenesis of aGVHD. Here, we show that PRMT5 expression and enzymatic activity were upregulated in activated T cells in vitro and in T cells from mice developing aGVHD after allogeneic transplant. PRMT5 expression was also upregulated in T cells of patients who developed aGVHD after allogeneic hematopoietic cell transplant compared with those who did not develop aGVHD. PRMT5 inhibition using a selective small-molecule inhibitor (C220) substantially reduced mouse and human allogeneic T cell proliferation and inflammatory IFN-γ and IL-17 cytokine production. Administration of PRMT5 small-molecule inhibitors substantially improves survival, reducing disease incidence and clinical severity in mouse models of aGVHD without adversely affecting engraftment. Importantly, we show that PRMT5 inhibition retained the beneficial graft-versus-leukemia effect by maintaining cytotoxic CD8+ T cell responses. Mechanistically, we show that PRMT5 inhibition potently reduced STAT1 phosphorylation as well as transcription of proinflammatory genes, including interferon-stimulated genes and IL-17. Additionally, PRMT5 inhibition deregulates the cell cycle in activated T cells and disrupts signaling by affecting ERK1/2 phosphorylation. Thus, we have identified PRMT5 as a regulator of T cell responses and as a therapeutic target in aGVHD.
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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.