ArticlePLoS pathogens2012
Redundant Notch1 and Notch2 signaling is necessary for IFNγ secretion by T helper 1 cells during infection with Leishmania major.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 78 citations in OpenAlex.
- miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology.Frontiers in immunology · 2018Trial
- Another Notch in the Belt of Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2024Review
- Canonical notch activation in patients with scrub typhus: association with organ dysfunction and poor outcome.Infection · 2024Article
- Runx3 Regulates CD8International journal of molecular sciences · 2024Article
- Notch signaling pathway involved inFrontiers in cellular and infection microbiology · 2023Article
- The potential value of Notch1 and DLL1 in the diagnosis and prognosis of patients with active TB.Frontiers in immunology · 2023Article
- Notch Signaling Promotes Mature T-Cell Lymphomagenesis.Cancer research · 2022Article
- A narrative review of the role of the Notch signaling pathway in rheumatoid arthritis.Annals of translational medicine · 2022Review
- Therapeutic Targeting of Notch Signaling: From Cancer to Inflammatory Disorders.Frontiers in cell and developmental biology · 2021Review
- GCNT1-MediatedJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- Differential immune response modulation in early Leishmania amazonensis infection of BALB/c and C57BL/6 macrophages based on transcriptome profiles.Scientific reports · 2019Article
- Notch signalling in T cell homeostasis and differentiation.Open biology · 2019Review
- [Role of the Notch signaling pathway in children with tuberculosis].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2019Article
- How Weird is The Worm? Evolution of the Developmental Gene Toolkit inJournal of developmental biology · 2019Review
- MiR-195 restrains lung adenocarcinoma by regulating CD4+ T cell activation via the CCDC88C/Wnt signaling pathway: a study based on the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and bioinformatic analysis.Annals of translational medicine · 2019Article
- Aggregation of Child Cardiac Progenitor Cells Into Spheres Activates Notch Signaling and Improves Treatment of Right Ventricular Heart Failure.Circulation research · 2019Article
- Notch Signaling Regulates Immune Responses in Atherosclerosis.Frontiers in immunology · 2019Review
- Adenosine A2A Receptor Stimulation Inhibits TCR-Induced Notch1 Activation in CD8+T-Cells.Frontiers in immunology · 2019Article
- Notch as an Immunologic Basis of Cancer Disparities.Cancer health disparities · 2019Article
- Notch signaling represents an important checkpoint between follicular T-helper and canonical T-helper 2 cell fate.Mucosal immunology · 2018Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The protective immune response to intracellular parasites involves in most cases the differentiation of IFNγ-secreting CD4(+) T helper (Th) 1 cells. Notch receptors regulate cell differentiation during development but their implication in the polarization of peripheral CD4(+) T helper 1 cells is not well understood. Of the four Notch receptors, only Notch1 (N1) and Notch2 (N2) are expressed on activated CD4(+) T cells. To investigate the role of Notch in Th1 cell differentiation following parasite infection, mice with T cell-specific gene ablation of N1, N2 or both (N1N2(ΔCD4Cre)) were infected with the protozoan parasite Leishmania major. N1N2(ΔCD4Cre) mice, on the C57BL/6 L. major-resistant genetic background, developed unhealing lesions and uncontrolled parasitemia. Susceptibility correlated with impaired secretion of IFNγ by draining lymph node CD4(+) T cells and increased secretion of the IL-5 and IL-13 Th2 cytokines. Mice with single inactivation of N1 or N2 in their T cells were resistant to infection and developed a protective Th1 immune response, showing that CD4(+) T cell expression of N1 or N2 is redundant in driving Th1 differentiation. Furthermore, we show that Notch signaling is required for the secretion of IFNγ by Th1 cells. This effect is independent of CSL/RBP-Jκ, the major effector of Notch receptors, since L. major-infected mice with a RBP-Jκ deletion in their T cells were able to develop IFNγ-secreting Th1 cells, kill parasites and heal their lesions. Collectively, we demonstrate here a crucial role for RBP-Jκ-independent Notch signaling in the differentiation of a functional Th1 immune response following L. major infection.
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