ArticleScience signaling2016
ROCK2 signaling is required to induce a subset of T follicular helper cells through opposing effects on STATs in autoimmune settings.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06046248 (Phase II Trial of Belumosudil and Rituximab for the Primary Treatment of Extensive Chronic Graft-versus-host Disease), which is not on this map. Cited by 38 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.
Phase II Trial of Belumosudil and Rituximab for the Primary Treatment of Extensive Chronic Graft-versus-host Disease
Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- Belumosudil reduces oral chronic graft-versus-host disease tissue inflammation and fibrosis: a ROCKstar companion study.Blood advances · 2025Trial
- A phase II study of belumosudil for chronic graft-versus-host disease in patients who failed at least one line of systemic therapy in China.BMC medicine · 2024Trial
- 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
- Belumosudil for acute GVHD after allogeneic hematopoietic stem cell transplantation: a retrospective case series.International journal of hematology · 2026Article
- Ruxolitinib-associated pulmonary alveolar proteinosis successfully managed by switching to belumosudil in chronic graft-versus-host disease.Blood cell therapy · 2026Article
- 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
- Patients with steroid-refractory gastrointestinal aGVHD respond to ROCK2 inhibitor rapidly.Annals of hematology · 2026Article
- ROCK signaling at the crossroads of redox stress, mitochondrial dynamics, and metabolic disease.Redox biology · 2026Review
- Article
- The role of BATF in immune cell differentiation and autoimmune diseases.Biomarker research · 2025Review
- ROCK 2 inhibition with belumosudil for the treatment of chronic graft-versus-host disease: a narrative review.Therapeutic advances in hematology · 2025Review
- Updates in chronic graft-versus-host disease: novel treatments and best practices in the current era.Bone marrow transplantation · 2024Review
- FUNDC1/PFKP-mediated mitophagy induced by KD025 ameliorates cartilage degeneration in osteoarthritis.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles Modulate Apoptosis, TNF Alpha and Interferon Gamma Response Gene mRNA Expression in T Lymphocytes.International journal of molecular sciences · 2023Article
- Human Effectors of Acute and Chronic GVHD Overexpress CD83 and Predict Mortality.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- ROCK2 inhibition attenuates profibrogenic immune cell function to reverse thioacetamide-induced liver fibrosis.JHEP reports : innovation in hepatology · 2022Article
- Insight Into Rho Kinase Isoforms in Obesity and Energy Homeostasis.Frontiers in endocrinology · 2022Review
- Critical regulation of follicular helper T cell differentiation and function by GαProceedings of the National Academy of Sciences of the United States of America · 2021Article
- ROCK2, a critical regulator of immune modulation and fibrosis has emerged as a therapeutic target in chronic graft-versus-host disease.Clinical immunology (Orlando, Fla.) · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Rho-associated kinase 2 (ROCK2) determines the balance between human T helper 17 (TH17) cells and regulatory T (Treg) cells. We investigated its role in the generation of T follicular helper (TFH) cells, which help to generate antibody-producing B cells under normal and autoimmune conditions. Inhibiting ROCK2 in normal human T cells or peripheral blood mononuclear cells from patients with active systemic lupus erythematosus (SLE) decreased the number and function of TFH cells induced by activation ex vivo. Moreover, inhibition of ROCK2 activity decreased the abundance of the transcriptional regulator Bcl6 (B cell lymphoma 6) and increased that of Blimp1 by reducing the binding of signal transducer and activator of transcription 3 (STAT3) and increasing that of STAT5 to the promoters of the genes Bcl6 and PRDM1, respectively. In the MRL/lpr murine model of SLE, oral administration of the selective ROCK2 inhibitor KD025 resulted in a twofold reduction in the numbers of TFH cells and antibody-producing plasma cells in the spleen, as well as a decrease in the size of splenic germinal centers, which are the sites of interaction between TFH cells and B cells. KD025-treated mice showed a substantial improvement in both histological and clinical scores compared to those of untreated mice and had reduced amounts of Bcl6 and phosphorylated STAT3, as well as increased STAT5 phosphorylation. Together, these data suggest that ROCK2 signaling plays a critical role in controlling the development of TFH cells induced by autoimmune conditions through reciprocal regulation of STAT3 and STAT5 activation.
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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.