ArticleThe Journal of clinical investigation2020
β1-Integrin- and KV1.3 channel-dependent signaling stimulates glutamate release from Th17 cells.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
- Targeting Metabolic Pathways to Direct T-Cell Trafficking: Therapeutic Perspectives.Biomedicines · 2026Review
- Immune-mediated excitotoxicity in brain disorders.Nature reviews. Immunology · 2026Review
- Role of CD5 signalling for pro-inflammatory Th17 response in multiple sclerosis.Brain : a journal of neurology · 2026Article
- Neurotransmitters as regulators of autoimmunity: mechanisms and translational targeting.NPJ autoimmunity · 2026Review
- Beta Integrin Expression Defines Functionally Distinct CD4Gastro hep advances · 2026Review
- Cdk5 regulates glutamine metabolism in colorectal cancer via the EZH2-GLS1 axis.Cancer & metabolism · 2025Article
- Development of a Human Preclinical Platform for the Identification of Neuroprotective Compounds.The European journal of neuroscience · 2025Article
- Identification of Novel Kv1.3 Channel-Interacting Proteins Using Proximity Labelling in T-Cells.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2025Article
- Exercise facilitates post-stroke recovery through mitigation of neuronal hyperexcitability via interleukin-10 signaling.Nature communications · 2025Article
- Flecainide mediated sodium channel blockade enhances blood brain barrier integrity and promotes neuroprotection in neuroinflammation.Scientific reports · 2025Article
- Distinct peripheral pro-inflammatory profile associated with tuberous sclerosis complex and epilepsy.Epilepsia · 2025Article
- Identification and development of TRPM4 antagonists to counteract neuronal excitotoxicity.iScience · 2024Article
- Metabolic footprint and logic through the T cell life cycle.Current opinion in immunology · 2024Review
- Proximity Labeling Proteomics Reveals Kv1.3 Potassium Channel Immune Interactors in Microglia.Molecular & cellular proteomics : MCP · 2024Article
- The neuropathobiology of multiple sclerosis.Nature reviews. Neuroscience · 2024Review
- Spatial transcriptomics and neurofilament light chain reveal changes in lesion patterns in murine autoimmune neuroinflammation.Journal of neuroinflammation · 2023Article
- Ameliorating Mitochondrial Dysfunction of Neurons by Biomimetic Targeting Nanoparticles Mediated Mitochondrial Biogenesis to Boost the Therapy of Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Implications of immunometabolism for smouldering MS pathology and therapy.Nature reviews. Neurology · 2023Review
- Non-conducting functions of ion channels: The case of integrin-ion channel complexes.Channels (Austin, Tex.) · 2022Review
- T-cell surveillance of the human brain in health and multiple sclerosis.Seminars in immunopathology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the impact of Th17 cells on autoimmunity is undisputable, their pathogenic effector mechanism is still enigmatic. We discovered soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) complex proteins in Th17 cells that enable a vesicular glutamate release pathway that induces local intracytoplasmic calcium release and subsequent damage in neurons. This pathway is glutamine dependent and triggered by binding of β1-integrin to vascular cell adhesion molecule 1 (VCAM-1) on neurons in the inflammatory context. Glutamate secretion could be blocked by inhibiting either glutaminase or KV1.3 channels, which are known to be linked to integrin expression and highly expressed on stimulated T cells. Although KV1.3 is not expressed in CNS tissue, intrathecal administration of a KV1.3 channel blocker or a glutaminase inhibitor ameliorated disability in experimental neuroinflammation. In humans, T cells from patients with multiple sclerosis secreted higher levels of glutamate, and cerebrospinal fluid glutamine levels were increased. Altogether, our findings demonstrate that β1-integrin- and KV1.3 channel-dependent signaling stimulates glutamate release from Th17 cells upon direct cell-cell contact between Th17 cells and neurons.
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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.