ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Regulation of Th1 cells and experimental autoimmune encephalomyelitis by glycogen synthase kinase-3.
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 50 papers.
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Who cites it
50 citing papers in PubMed, 86 citations in OpenAlex.
- The Neurovascular Niche: A Gathering Venue for Neuroinflammation and Remyelination in Multiple Sclerosis.Acta physiologica (Oxford, England) · 2026Review
- Probing Allosteric Kinase Modulators as Next Game-Changers in Fighting Neurodegeneration.Journal of medicinal chemistry · 2026Review
- Interleukin-16 enhances anti-tumor immune responses by establishing a Th1 cell-macrophage crosstalk through reprogramming glutamine metabolism in mice.Nature communications · 2025Article
- Multiscale networks in multiple sclerosis.PLoS computational biology · 2024Article
- Low Doses of β-Caryophyllene Reduced Clinical and Paraclinical Parameters of an Autoimmune Animal Model of Multiple Sclerosis: Investigating the Role of CBBrain sciences · 2023Article
- GSK-3β Allosteric Inhibition: A Dead End or a New Pharmacological Frontier?International journal of molecular sciences · 2023Review
- New insights into the role of GSK-3β in the brain: from neurodegenerative disease to tumorigenesis.PeerJ · 2023Review
- The Dual PDE7-GSK3β Inhibitor, VP3.15, as Neuroprotective Disease-Modifying Treatment in a Model of Primary Progressive Multiple Sclerosis.International journal of molecular sciences · 2022Article
- Gut Barrier Dysfunction and Type 2 Immunity: Implications for Compulsive Behavior.Medical hypotheses · 2022Article
- Revisiting the Role of GSK3, A Modulator of Innate Immunity, in Idiopathic Inclusion Body Myositis.Cells · 2021Review
- Glycogen synthase kinase 3 drives thymocyte egress by suppressing β-catenin activation of Akt.Science advances · 2021Article
- Glycogen Synthase Kinase-3: A Focal Point for Advancing Pathogenic Inflammation in Depression.Cells · 2021Review
- GSK-3β, FYN, and DYRK1A: Master Regulators in Neurodegenerative Pathways.International journal of molecular sciences · 2021Review
- Allosteric Modulation of GSK-3β as a New Therapeutic Approach in Limb Girdle Muscular Dystrophy R1 Calpain 3-Related.International journal of molecular sciences · 2021Article
- Article
- Dynamics of Central Remyelination and Treatment Evolution in a Model of Multiple Sclerosis with Optic Coherence Tomography.International journal of molecular sciences · 2021Article
- Review
- Glycogen Synthase Kinase-3 Inhibitors: Preclinical and Clinical Focus on CNS-A Decade Onward.Frontiers in molecular neuroscience · 2021Review
- Discovery and Design of Novel Small Molecule GSK-3 Inhibitors Targeting the Substrate Binding Site.International journal of molecular sciences · 2020Article
- Glycogen synthase kinase-3 promotes T helper type 17 differentiation by promoting interleukin-9 production.Immunology · 2020Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
Experimental autoimmune encephalomyelitis (EAE) is a rodent model of multiple sclerosis (MS), a debilitating autoimmune disease of the CNS, for which only limited therapeutic interventions are available. Because MS is mediated in part by autoreactive T cells, particularly Th17 and Th1 cells, in the current study, we tested whether inhibitors of glycogen synthase kinase-3 (GSK3), previously reported to reduce Th17 cell generation, also alter Th1 cell production or alleviate EAE. GSK3 inhibitors were found to impede the production of Th1 cells by reducing STAT1 activation. Molecularly reducing the expression of either of the two GSK3 isoforms demonstrated that Th17 cell production was sensitive to reduced levels of GSK3β and Th1 cell production was inhibited in GSK3α-deficient cells. Administration of the selective GSK3 inhibitors TDZD-8, VP2.51, VP0.7, or L803-mts significantly reduced the clinical symptoms of myelin oligodendrocyte glycoprotein35-55-induced EAE in mice, nearly eliminating the chronic progressive phase, and reduced the number of Th17 and Th1 cells in the spinal cord. Administration of TDZD-8 or L803-mts after the initial disease episode alleviated clinical symptoms in a relapsing-remitting model of proteolipid protein139-151-induced EAE. Furthermore, deletion of GSK3β specifically in T cells was sufficient to alleviate myelin oligodendrocyte glycoprotein35-55-induced EAE. These results demonstrate the isoform-selective effects of GSK3 on T cell generation and the therapeutic effects of GSK3 inhibitors in EAE, as well as showing that GSK3 inhibition in T cells is sufficient to reduce the severity of EAE, suggesting that GSK3 may be a feasible target for developing new therapeutic interventions for MS.
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Registered trials
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