ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Notch signaling regulates T cell accumulation and function in the central nervous system during experimental autoimmune encephalomyelitis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Identification of a novel genetic locus associated with immune-mediated thrombotic thrombocytopenic purpura.Haematologica · 2022Pooled it
- S3I-201, a STAT3 Inhibitor, Inhibits Proinflammatory Mediator Signalling in CD19 and CD45R/B220 Cells in a Mouse Model of Multiple Sclerosis.Cellular and molecular neurobiology · 2026Article
- Notch3 destabilizes regulatory T cells to drive autoimmune neuroinflammation in multiple sclerosis.Immunity · 2025Article
- DAPTA, a C-C Chemokine Receptor 5 (CCR5), Leads to the Downregulation of Notch/NF-κB Signaling and Proinflammatory Mediators in CD40Biomedicines · 2023Article
- Roles of Notch Signaling in the Tumor Microenvironment.International journal of molecular sciences · 2022Review
- A narrative review of the role of the Notch signaling pathway in rheumatoid arthritis.Annals of translational medicine · 2022Review
- Vascular smooth muscle cell dysfunction in neurodegeneration.Frontiers in neuroscience · 2022Review
- Article
- Therapeutic Targeting of Notch Signaling: From Cancer to Inflammatory Disorders.Frontiers in cell and developmental biology · 2021Review
- Post-Developmental Roles of Notch Signaling in the Nervous System.Biomolecules · 2020Review
- GCNT1-MediatedJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- Notch signalling in T cell homeostasis and differentiation.Open biology · 2019Review
- Notch-1 Inhibition Promotes Immune Regulation in Transplantation Via Regulatory T Cell-Dependent Mechanisms.Circulation · 2019Article
- Early Notch Signals Induce a Pathogenic Molecular Signature during Priming of Alloantigen-Specific Conventional CD4Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Notch ligand Delta-like 4 induces epigenetic regulation of Treg cell differentiation and function in viral infection.Mucosal immunology · 2018Article
- Presenilin1 regulates Th1 and Th17 effector responses but is not required for experimental autoimmune encephalomyelitis.PloS one · 2018Article
- Article
- T Cell-Restricted Notch Signaling Contributes to Pulmonary Th1 and Th2 Immunity duringJournal of immunology (Baltimore, Md. : 1950) · 2017Article
- IL-17 induced NOTCH1 activation in oligodendrocyte progenitor cells enhances proliferation and inflammatory gene expression.Nature communications · 2017Article
- Notch Ligand Delta-like 4 Promotes Regulatory T Cell Identity in Pulmonary Viral Infection.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Systemic inhibition of Notch signaling was previously shown to attenuate experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis in mice. Different studies attributed these effects to decreased T-bet and IFN-γ expression, enhanced regulatory T cell function, reduced T cell chemotaxis to the CNS, or impaired Th9 cell differentiation. Interpretation of these heterogeneous findings is difficult because past experimental strategies did not ensure complete Notch inhibition in T cells and because many cell populations could be affected by systemic Notch blockade. To resolve the role of Notch in T cells during EAE, we used the pan-Notch inhibitor dominant-negative form of Mastermind-like 1 (DNMAML), as well as several complementary loss-of-function approaches specifically in myelin-reactive T cells. Notch inhibition in T cells profoundly decreased EAE incidence and severity. Notch-deprived myelin-reactive T cells had preserved activation and effector differentiation in secondary lymphoid tissues. However, Notch-deprived T cells failed to accumulate in the CNS after immunization. Parking wild-type and DNMAML T cells together in bone marrow chimeras increased accumulation of Notch-deprived T cells in the CNS after immunization but did not prevent EAE, indicating the absence of dominant suppression by DNMAML T cells. Analysis of CNS-infiltrating DNMAML T cells revealed markedly defective IL-17A and IFN-γ production, despite preserved T-bet expression. Collectively, our findings capture the profound overall effects of Notch signaling in myelin-reactive T cells and demonstrate that Notch controls the accumulation and pathogenic functions of CD4(+) T cells within their target organ but not in lymphoid tissues during EAE.
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Registered trials
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