ArticleAnnals of the rheumatic diseases2017
Targeting the RhoA-ROCK pathway to reverse T-cell dysfunction in SLE.
Article in Annals of the rheumatic diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Pooled it
- Belumosudil reduces oral chronic graft-versus-host disease tissue inflammation and fibrosis: a ROCKstar companion study.Blood advances · 2025Trial
- Nasal administration of anti-CD3 mAb (Foralumab) downregulatesProceedings of the National Academy of Sciences of the United States of America · 2023Trial
- Geranylgeranylation is required for B-cell proliferation and plasma cell survival implications for autoimmune therapy.Cellular & molecular immunology · 2026Article
- Lipid metabolism in homeostasis and disease.Signal transduction and targeted therapy · 2026Review
- Natural products as HMG-CoA reductase inhibitors (statins) for the management of non-communicable diseases.Inflammopharmacology · 2026Review
- Specific macrophage RhoA targeting CRISPR-Cas9 for mitigating osteoclastogenesis-induced joint damage in inflammatory arthritis.Cell reports. Medicine · 2025Article
- TAGLN-RhoA/ROCK2-SLC2A3-mediated Mechano-metabolic Axis Promotes Skin Fibrosis.International journal of biological sciences · 2025Article
- First-in-human study of CPL'116 - a dual JAK/ROCK inhibitor - in healthy subjects.Frontiers in pharmacology · 2025Article
- Updates in chronic graft-versus-host disease: novel treatments and best practices in the current era.Bone marrow transplantation · 2024Review
- Potential role of RhoA GTPase regulation in type interferon signaling in systemic lupus erythematosus.Arthritis research & therapy · 2024Article
- FUNDC1/PFKP-mediated mitophagy induced by KD025 ameliorates cartilage degeneration in osteoarthritis.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- SUMOylation of Rho-associated protein kinase 2 induces goblet cell metaplasia in allergic airways.Nature communications · 2023Article
- Advantages of Rho-associated kinases and their inhibitor fasudil for the treatment of neurodegenerative diseases.Neural regeneration research · 2022Review
- Formulary Drug Review: Belumosudil.Hospital pharmacy · 2022Review
- Rho GTPase signaling in rheumatic diseases.iScience · 2022Review
- Rho GTPases in kidney physiology and diseases.Small GTPases · 2022Article
- Insight Into Rho Kinase Isoforms in Obesity and Energy Homeostasis.Frontiers in endocrinology · 2022Review
- QRISK3-based analysis of cardiovascular risk factors in patients with long-term but well-controlled systemic lupus erythematosus.American journal of translational research · 2022Article
- Strategies of Targeting Inflammasome in the Treatment of Systemic Lupus Erythematosus.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesDeregulated production of interleukin (IL)-17 and IL-21 contributes to the pathogenesis of autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Production of IL-17 and IL-21 can be regulated by ROCK2, one of the two Rho kinases. Increased ROCK activation was previously observed in an SLE cohort. Here, we evaluated ROCK activity in a new SLE cohort, and an RA cohort, and assessed the ability of distinct inhibitors of the ROCK pathway to suppress production of IL-17 and IL-21 by SLE T cells or human Th17 cells.
methodsROCK activity in peripheral blood mononuclear cells (PBMCs) from 29 patients with SLE, 31 patients with RA and 28 healthy controls was determined by ELISA. SLE T cells or in vitro-differentiated Th17 cells were treated with Y27632 (a pan-ROCK inhibitor), KD025 (a selective ROCK2 inhibitor) or simvastatin (which inhibits RhoA, a major ROCK activator). ROCK activity and IL-17 and IL-21 production were assessed. The transcriptional profile altered by ROCK inhibitors was evaluated by NanoString technology.
resultsROCK activity levels were significantly higher in patients with SLE and RA than healthy controls. Th17 cells exhibited high ROCK activity that was inhibited by Y27632, KD025 or simvastatin; each also decreased IL-17 and IL-21 production by purified SLE T cells or Th17 cells. Immune profiling revealed both overlapping and distinct effects of the different ROCK inhibitors.
conclusionsROCK activity is elevated in PBMCs from patients with SLE and RA. Production of IL-17 and IL-21 by SLE T cells or Th17 cells can furthermore be inhibited by targeting the RhoA-ROCK pathway via both non-selective and selective approaches.
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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.