ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Proprotein convertase FURIN constrains Th2 differentiation and is critical for host resistance against Toxoplasma gondii.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
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- Ethyl acetate extract of fungus comb from Malayan termite (Open veterinary journal · 2024Article
- Molecular regulation of NLRP3 inflammasome activation during parasitic infection.Bioscience reports · 2024Review
- The possible role furin and furin inhibitors in endometrial adenocarcinoma: A narrative review.Cancer reports (Hoboken, N.J.) · 2024Review
- PIM kinases regulate early human Th17 cell differentiation.Cell reports · 2023Article
- Could a Lower Toll-like Receptor (TLR) and NF-κB Activation Due to a Changed Charge Distribution in the Spike Protein Be the Reason for the Lower Pathogenicity of Omicron?International journal of molecular sciences · 2022Review
- A perspective on the applications of furin inhibitors for the treatment of SARS-CoV-2.Pharmacological reports : PR · 2022Article
- Cluster analysis of splenocyte microRNAs in the pig reveals key signal regulators of immunomodulation in the host during acute and chronic Toxoplasma gondii infection.Parasites & vectors · 2022Article
- Therapeutic anti-glioma effect of the combined action of PCSK inhibitor with the anti-tumoral factors secreted by Poly (I:C)-stimulated macrophages.Cancer gene therapy · 2022Article
- Article
- The proprotein convertase furin inhibits IL-13-induced inflammation in airway smooth muscle by regulating integrin-associated signaling complexes.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- Identification of Novel Genetic Regulatory Region for Proprotein Convertase FURIN and Interferon Gamma in T Cells.Frontiers in immunology · 2021Article
- T-Cell Hyperactivation and Paralysis in Severe COVID-19 Infection Revealed by Single-Cell Analysis.Frontiers in immunology · 2020Article
- Article
- Lack of p53 Augments Antitumor Functions in Cytolytic T Cells.Cancer research · 2016Article
- Article
- T-cell-expressed proprotein convertase FURIN inhibits DMBA/TPA-induced skin cancer development.OncoimmunologyArticle
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
The proprotein convertase subtilisin/kexin enzymes proteolytically convert immature proproteins into bioactive molecules, and thereby they serve as key regulators of cellular homeostasis. The archetype proprotein convertase subtilisin/kexin, FURIN, is a direct target gene of the IL-12/STAT4 pathway and it is upregulated in Th1 cells. We have previously demonstrated that FURIN expression in T cells critically regulates the maintenance of peripheral immune tolerance and the functional maturation of pro-TGF-β1 in vivo, but FURIN's role in cell-mediated immunity and Th polarization has remained elusive. In this article, we show that T cell-expressed FURIN is essential for host resistance against a prototypic Th1 pathogen, Toxoplasma gondii, and for the generation of pathogen-specific Th1 lymphocytes, including Th1-IL-10 cells. FURIN-deficient Th cells instead show elevated expression of IL-4R subunit α on cell surface, sensitized IL-4/STAT6 signaling, and a propensity to polarize toward the Th2 phenotype. By exploring FURIN-interacting proteins in Jurkat T cells with Strep-Tag purification and mass spectrometry, we further identify an association with a cytoskeleton modifying Ras-related C3 botulinum toxin substrate/dedicator of cytokinesis 2 protein complex and unravel that FURIN promotes F-actin polymerization, which has previously been shown to downregulate IL-4R subunit α cell surface expression and promote Th1 responses. In conclusion, our results demonstrate that in addition to peripheral immune tolerance, T cell-expressed FURIN is also a central regulator of cell-mediated immunity and Th1/2 cell balance.
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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.