ArticleBlood2020
JAK/STAT pathway inhibition sensitizes CD8 T cells to dexamethasone-induced apoptosis in hyperinflammation.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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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
51 citing papers in PubMed, 101 citations in OpenAlex.
- HLHRUXO: a prospective trial of a ruxolitinib-containing regimen for children with hemophagocytic lymphohistiocytosis.Blood advances · 2026Trial
- Ruxolitinib plus standard of care in severe hospitalized adults with severe fever with thrombocytopenia syndrome (SFTS): an exploratory, single-arm trial.BMC medicine · 2024Trial
- Dose-escalating ruxolitinib for refractory hemophagocytic lymphohistiocytosis.Frontiers in immunology · 2023Trial
- Apatinib resistance mediated by IRF9 nuclear translocation in head and neck squamous cell carcinoma.iScience · 2026Article
- [Mechanism and clinical progress of JAK inhibitors in hemophagocytic lymphohistiocytosis].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Review
- Hypothesis-driven salvage therapy with corticosteroids, tofacitinib, and nintedanib for progressive radiation pneumonitis with possible immune-mediated contribution: a case report.Frontiers in immunology · 2026Article
- Histiocyte Society blueprint for hemophagocytic lymphohistiocytosis research: deciphering underlying disease mechanisms to optimize diagnosis and therapy.Haematologica · 2025Review
- RSL3 promotes PARP1 apoptotic functions by distinct mechanisms during ferroptosis.Cellular & molecular biology letters · 2025Article
- Celastrol inhibits the DPYSL2-JAK/STAT pathway by targeting mito-IDHs mediated mitochondrial metabolism to exhaust breast cancer.Acta pharmacologica Sinica · 2025Article
- Cytokine Storm Induction Linked to Multi-Organ Failure in Fatal Jellyfish Stings.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mucosal implications of oral Jak3-targeted drugs in COVID patients.Molecular medicine (Cambridge, Mass.) · 2025Review
- Deep insight into cytokine storm: from pathogenesis to treatment.Signal transduction and targeted therapy · 2025Review
- Article
- Individualized therapy guided by single-cell sequencing in anti-GABATranslational psychiatry · 2025Article
- CXCL9 and IL-18: potential biomarkers for efficacy evaluation in refractory hemophagocytic lymphohistiocytosis treated with RED (ruxolitinib, emapalumab and dexamethasone).Annals of hematology · 2025Article
- Comprehensive bioinformatics analysis identifies hub genes associated with immune cell infiltration in early-onset schizophrenia.BMC psychiatry · 2025Article
- Primary prostatic Burkitt's lymphoma complicated with hemophagocytic lymphohistiocytosis: a case report and literature review.Frontiers in oncology · 2025Article
- Plausible mechanism of drug resistance and side-effects of COVID-19 therapeutics: a bottleneck for its eradication.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2024Review
- Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms.Journal of hematology & oncology · 2024Review
- Exosomes as promising bioactive materials in the treatment of spinal cord injury.Stem cell research & therapy · 2024Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Cytokine storm syndromes (CSS) are severe hyperinflammatory conditions characterized by excessive immune system activation leading to organ damage and death. Hemophagocytic lymphohistiocytosis (HLH), a disease often associated with inherited defects in cell-mediated cytotoxicity, serves as a prototypical CSS for which the 5-year survival is only 60%. Frontline therapy for HLH consists of the glucocorticoid dexamethasone (DEX) and the chemotherapeutic agent etoposide. Many patients, however, are refractory to this treatment or relapse after an initial response. Notably, many cytokines that are elevated in HLH activate the JAK/STAT pathway, and the JAK1/2 inhibitor ruxolitinib (RUX) has shown efficacy in murine HLH models and humans with refractory disease. We recently reported that cytokine-induced JAK/STAT signaling mediates DEX resistance in T cell acute lymphoblastic leukemia (T-ALL) cells, and that this could be effectively reversed by RUX. On the basis of these findings, we hypothesized that cytokine-mediated JAK/STAT signaling might similarly contribute to DEX resistance in HLH, and that RUX treatment would overcome this phenomenon. Using ex vivo assays, a murine model of HLH, and primary patient samples, we demonstrate that the hypercytokinemia of HLH reduces the apoptotic potential of CD8 T cells leading to relative DEX resistance. Upon exposure to RUX, this apoptotic potential is restored, thereby sensitizing CD8 T cells to DEX-induced apoptosis in vitro and significantly reducing tissue immunopathology and HLH disease manifestations in vivo. Our findings provide rationale for combining DEX and RUX to enhance the lymphotoxic effects of DEX and thus improve the outcomes for patients with HLH and related CSS.
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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.