ArticleThe Journal of experimental medicine2013
Therapeutic targeting of NOTCH signaling ameliorates immune-mediated bone marrow failure of aplastic anemia.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 85 citations in OpenAlex.
- T Cell Transcriptomes from Paroxysmal Nocturnal Hemoglobinuria Patients Reveal Novel Signaling Pathways.Journal of immunology (Baltimore, Md. : 1950) · 2017Trial
- Targeting interleukin-2-inducible T cell kinase ameliorates immune-mediated aplastic anemia.Cancer immunology, immunotherapy : CII · 2025Article
- Potential of ginsenoside Rg1 to treat aplastic anemiaWorld journal of stem cells · 2024Article
- Combating bone marrow failure with polymer materials.Frontiers in immunology · 2024Review
- Mechanisms and biomarkers of immune-related adverse events in gastric cancer.European journal of medical research · 2023Review
- Increased Expression of NOTCH-1 and T Helper Cell Transcription Factors in Patients with Acquired Aplastic Anemia.Iranian biomedical journal · 2023Article
- Mechanism of TCF21 Downregulation Leading to Immunosuppression of Tumor-Associated Macrophages in Non-Small Cell Lung Cancer.Pharmaceutics · 2023Article
- Article
- PRMT5 regulates epigenetic changes in suppressive Th1-like iTregs in response to IL-12 treatment.Frontiers in immunology · 2023Article
- [Kinetics of immune activated T cells in aplastic anemia mouse model].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2022Article
- CCR5 maintains macrophages in the bone marrow and drives hematopoietic failure in a mouse model of severe aplastic anemia.Leukemia · 2021Article
- Identification of NOTCH4 mutation as a response biomarker for immune checkpoint inhibitor therapy.BMC medicine · 2021Article
- More Insights on the Use of γ-Secretase Inhibitors in Cancer Treatment.The oncologist · 2021Article
- Therapeutic Targeting of Notch Signaling: From Cancer to Inflammatory Disorders.Frontiers in cell and developmental biology · 2021Review
- T-cell expression of Bruton's tyrosine kinase promotes autoreactive T-cell activation and exacerbates aplastic anemia.Cellular & molecular immunology · 2020Article
- Efficacy of immunotherapy in lung cancer with co-occurring mutations in NOTCH and homologous repair genes.Journal for immunotherapy of cancer · 2020Article
- GCNT1-MediatedJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- Notch 1 Is Involved in CD4Frontiers in cellular and infection microbiology · 2020Article
- Notch signalling in T cell homeostasis and differentiation.Open biology · 2019Review
- [Tetramethylpyrazine promotes bone marrow repair in a C57 mouse model of X-rayinduced immune-mediated bone marrow failure].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2019Article
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 2 countries.
Funding
Abstract
Severe aplastic anemia (AA) is a bone marrow (BM) failure (BMF) disease frequently caused by aberrant immune destruction of blood progenitors. Although a Th1-mediated pathology is well described for AA, molecular mechanisms driving disease progression remain ill defined. The NOTCH signaling pathway mediates Th1 cell differentiation in the presence of polarizing cytokines, an action requiring enzymatic processing of NOTCH receptors by γ-secretase. Using a mouse model of AA, we demonstrate that expression of both intracellular NOTCH1(IC) and T-BET, a key transcription factor regulating Th1 cell differentiation, was increased in spleen and BM-infiltrating T cells during active disease. Conditionally deleting Notch1 or administering γ-secretase inhibitors (GSIs) in vivo attenuated disease and rescued mice from lethal BMF. In peripheral T cells from patients with untreated AA, NOTCH1(IC) was significantly elevated and bound to the TBX21 promoter, showing NOTCH1 directly regulates the gene encoding T-BET. Treating patient cells with GSIs in vitro lowered NOTCH1(IC) levels, decreased NOTCH1 detectable at the TBX21 promoter, and decreased T-BET expression, indicating that NOTCH1 signaling is responsive to GSIs during active disease. Collectively, these results identify NOTCH signaling as a primary driver of Th1-mediated pathogenesis in AA and may represent a novel target for therapeutic intervention.
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