ArticleThe Journal of clinical investigation2022
The druggable transcription factor Fli-1 regulates T cell immunity and tolerance in graft-versus-host disease.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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
16 citing papers in PubMed, 33 citations in OpenAlex.
- Trial
- STUB1-mediated ubiquitination regulates Fli-1 stability and CD4⁺T cell activation during inflammation.Molecular medicine (Cambridge, Mass.) · 2026Article
- Cross-platform transcriptomic data integration identifies an overactive neuro-immune signature in human osteoarthritis synovium.Osteoarthritis and cartilage · 2026Article
- A convenient single-cell assay for the newly synthesized transcriptome reveals FLI1 regulon downregulation during T cell activation.Cell reports methods · 2026Article
- Lichenoid graft-versus-host disease shows a high interferon score, with IFNAR1 inhibition preventing skin inflammation.Journal of the European Academy of Dermatology and Venereology : JEADV · 2025Article
- Growth of human regulatory CD4iScience · 2025Article
- A novel deep learning framework with dynamic tokenization for identifying chromatin interactions along with motif importance investigation.Briefings in bioinformatics · 2025Article
- Role of Transcription Factor Fli-1 in Inflammation and Autoimmune Diseases.Biomolecules · 2025Review
- Oxidative phosphorylation is a key feature of neonatal monocyte immunometabolism promoting myeloid differentiation after birth.Nature communications · 2025Article
- FLI1 Induces Plaque Psoriasis and Its Inhibition Attenuates Disease Progression.Journal of inflammation research · 2025Article
- Immunocyte lipid metabolic reprogramming: a novel pathway for targeted intervention in autoimmune diseases.Frontiers in immunology · 2025Review
- FLI-1-driven regulation of endothelial cells in human diseases.Journal of translational medicine · 2024Review
- Functional CRISPR screens in T cells reveal new opportunities for cancer immunotherapies.Molecular cancer · 2024Review
- FLI1 induces erythroleukemia through opposing effects on UBASH3A and UBASH3B expression.BMC cancer · 2024Article
- FLI1 in PBMCs contributes to elevated inflammation in combat-related posttraumatic stress disorder.Frontiers in psychiatry · 2024Article
- Dissecting the regulatory network of transcription factors in T cell phenotype/functioning during GVHD and GVT.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Graft-versus-host disease (GVHD), manifesting as either acute (aGVHD) or chronic (cGVHD), presents significant life-threatening complications following allogeneic hematopoietic cell transplantation. Here, we investigated Friend virus leukemia integration 1 (Fli-1) in GVHD pathogenesis and validated Fli-1 as a therapeutic target. Using genetic approaches, we found that Fli-1 dynamically regulated different T cell subsets in allogeneic responses and pathogenicity in the development of aGVHD and cGVHD. Compared with homozygous Fli1-deficient or WT T cells, heterozygous Fli1-deficient T cells induced the mildest GVHD, as evidenced by the lowest Th1 and Th17 cell differentiation. Single-cell RNA-Seq analysis revealed that Fli-1 differentially regulated CD4+ and CD8+ T cell responses. Fli-1 promoted the transcription of Th1/Th17 pathways and T cell receptor-inducible (TCR-inducible) transcription factors in CD4+ T cells, while suppressing activation- and function-related gene pathways in CD8+ T cells. Importantly, a low dose of camptothecin, topotecan, or etoposide acted as a potent Fli-1 inhibitor and significantly attenuated GVHD severity, while preserving the graft-versus-leukemia (GVL) effect. This observation was extended to a xenograft model, in which GVHD was induced by human T cells. In conclusion, we provide evidence that Fli-1 plays a crucial role in alloreactive CD4+ T cell activation and differentiation and that targeting Fli-1 may be an attractive strategy for treating GVHD without compromising the GVL effect.
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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 Socratic graph.