ArticleThe Journal of clinical investigation2010
Phosphorylation of IRF4 by ROCK2 regulates IL-17 and IL-21 production and the development of autoimmunity in mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
133 citing papers in PubMed, 1 synthesis or guideline pooled it, 234 citations in OpenAlex.
- Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity.Nature genetics · 2012Pooled it
- Novel highly selective ROCK2 inhibitor (TDI01) for the treatment of chronic graft-versus-host disease: a multicenter, open-label phase Ib/II study.Signal transduction and targeted therapy · 2026Trial
- Belumosudil reduces oral chronic graft-versus-host disease tissue inflammation and fibrosis: a ROCKstar companion study.Blood advances · 2025Trial
- Cutting Edge: Selective Oral ROCK2 Inhibitor Reduces Clinical Scores in Patients with Psoriasis Vulgaris and Normalizes Skin Pathology via Concurrent Regulation of IL-17 and IL-10.Journal of immunology (Baltimore, Md. : 1950) · 2017Trial
- Molecular Signature and miRNA Pattern of CD4 + T Lymphocytes in Plaque Psoriasis.Clinical reviews in allergy & immunology · 2026Review
- ROCK2 inhibition suppresses cytotoxic T lymphocyte-mediated platelet destruction in primary immune thrombocytopenia.Cell & bioscience · 2026Article
- Chronic graft-versus-host disease.Nature reviews. Disease primers · 2026Review
- Interferon regulatory factor 4 as a context-dependent regulator of inflammation: transcriptional and epigenetic control, skin diseases, and translational challenges.Frontiers in immunology · 2026Review
- Regulatory Immune Cell-derived Exosomes: Modes of Action and Therapeutic Potential in Transplantation.Transplantation · 2025Review
- Anti-inflammatory actions of ripasudil ameliorate experimental autoimmune uveoretinitis in the acute phase.BMJ open ophthalmology · 2025Article
- ROCK1 promotes B cell differentiation and proteostasis under stress through the heme-regulated proteins, BACH2 and HRI.JCI insight · 2025Article
- Characterization of T-bet expressing B cells in lupus patients indicates a putative prognostic and therapeutic value of these cells for the disease.Clinical and experimental immunology · 2025Article
- ROCK 2 inhibition with belumosudil for the treatment of chronic graft-versus-host disease: a narrative review.Therapeutic advances in hematology · 2025Review
- Emerging Role of NAT10 as ac4C Writer in Inflammatory Diseases: Mechanisms and Therapeutic Applications.Current drug targets · 2025Review
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Article
- IRF4 Participates in Pulmonary Fibrosis Induced by Silica Particles through Regulating Macrophage Polarization and Fibroblast Activation.Inflammation · 2024Article
- Potential role of RhoA GTPase regulation in type interferon signaling in systemic lupus erythematosus.Arthritis research & therapy · 2024Article
- ROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease.Nature communications · 2024Article
- Transcription Factor IRF7 is Involved in Psoriasis Development and Response to Guselkumab Treatment.Journal of inflammation research · 2024Article
73 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Deregulated production of IL-17 and IL-21 plays a key pathogenic role in many autoimmune disorders. A delineation of the mechanisms that underlie the inappropriate synthesis of IL-17 and IL-21 in autoimmune diseases can thus provide important insights into potential therapies for these disorders. Here we have shown that the serine-threonine kinase Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2) becomes activated in mouse T cells under Th17 skewing conditions and phosphorylates interferon regulatory factor 4 (IRF4), a transcription factor that is absolutely required for the production of IL-17 and IL-21. We furthermore demonstrated that ROCK2-mediated phosphorylation of IRF4 regulated the synthesis of IL-17 and IL-21 and the differentiation of Th17 cells. Whereas CD4+ T cells from WT mice activated ROCK2 physiologically under Th17 conditions, CD4+ T cells from 2 different mouse models of spontaneous autoimmunity aberrantly activated ROCK2 under neutral conditions. Moreover, administration of ROCK inhibitors ameliorated the deregulated production of IL-17 and IL-21 and the inflammatory and autoantibody responses observed in these autoimmune mice. Our findings thus uncover a crucial link among ROCK2, IRF4, and the production of IL-17 and IL-21 and support the idea that selective inhibition of ROCK2 could represent an important therapeutic regimen for the treatment of autoimmune disorders.
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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.