ArticleNature communications2024
ROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 10 citations in OpenAlex.
- Efficacy and safety of the ROCK2-inhibitor belumosudil for chronic GVHD: results from a multicenter retrospective analysis of a large German-Austrian cohort of the belumosudil MAP.Bone marrow transplantation · 2026Article
- Pegtarazimod limits acute graft-versus-host disease mortality and severity in mice and is tolerated in patients.The Journal of clinical investigation · 2026Article
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- Belumosudil for acute GVHD after allogeneic hematopoietic stem cell transplantation: a retrospective case series.International journal of hematology · 2026Article
- BCL2 overexpression in donor lymphocytes reduces the risk of graft-versus-host disease.Blood advances · 2026Article
- Patients with steroid-refractory gastrointestinal aGVHD respond to ROCK2 inhibitor rapidly.Annals of hematology · 2026Article
- Article
- Identifying Biomedical Entities for Datasets in Scientific Articles: 4-Step Cache-Augmented Generation Approach Using GPT-4o and PubTator 3.0.JMIR formative research · 2025Article
- Causal Effect of Blood Cell Perturbation Phenotypes on Multiple Sclerosis via Immune Mediation: A Mendelian Randomization Study.Cellular and molecular neurobiology · 2025Article
- Interleukin Networks in GVHD: Mechanistic Crosstalk, Therapeutic Targeting, and Emerging Paradigms.International journal of molecular sciences · 2025Review
- [Effectiveness and safety of belumosudil in 20 patients with chronic graft-versus-host disease].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Article
- FDA-approved therapies for chronic GVHD.Blood · 2025Review
- Graft-Versus-Host Disease Mouse Models: A Clinical-Translational Perspective.Methods in molecular biology (Clifton, N.J.) · 2025Review
Corrections and comments
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Authors and funding
43 authors at 6 institutions in 3 countries.
Funding
Abstract
Patients with corticosteroid-refractory acute graft-versus-host disease (aGVHD) have a low one-year survival rate. Identification and validation of novel targetable kinases in patients who experience corticosteroid-refractory-aGVHD may help improve outcomes. Kinase-specific proteomics of leukocytes from patients with corticosteroid-refractory-GVHD identified rho kinase type 1 (ROCK1) as the most significantly upregulated kinase. ROCK1/2 inhibition improved survival and histological GVHD severity in mice and was synergistic with JAK1/2 inhibition, without compromising graft-versus-leukemia-effects. ROCK1/2-inhibition in macrophages or dendritic cells prior to transfer reduced GVHD severity. Mechanistically, ROCK1/2 inhibition or ROCK1 knockdown interfered with CD80, CD86, MHC-II expression and IL-6, IL-1β, iNOS and TNF production in myeloid cells. This was accompanied by impaired T cell activation by dendritic cells and inhibition of cytoskeletal rearrangements, thereby reducing macrophage and DC migration. NF-κB signaling was reduced in myeloid cells following ROCK1/2 inhibition. In conclusion, ROCK1/2 inhibition interferes with immune activation at multiple levels and reduces acute GVHD while maintaining GVL-effects, including in corticosteroid-refractory settings.
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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.