ArticlePloS one2015
Microglia Induce Neurotoxic IL-17+ γδ T Cells Dependent on TLR2, TLR4, and TLR9 Activation.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 58 citations in OpenAlex.
- Review
- The Role of γδ T Cells in Ischemic Stroke: Insights From the Perspective of the Brain-Gut Axis.CNS neuroscience & therapeutics · 2026Review
- MicroRNA-29a-5p contributes to neuroinflammation through TLR7.Journal of neuroinflammation · 2026Article
- Cytotoxic T lymphocytes and their dual role in modulating blood-brain barrier integrity in immune-mediated neurological pathologies.Journal of translational medicine · 2025Review
- Interleukin-17A signaling promotes CD8+ T cell cytotoxicity against West Nile virus infection through enhancing PI3K-mTOR-mediated metabolism.PLoS pathogens · 2025Article
- T cell receptor activation contributes to brain damage after intracerebral hemorrhage in mice.Journal of neuroinflammation · 2025Article
- Divergent Crosstalk Between Microglia and T Cells in Brain Cancers: Implications for Novel Therapeutic Strategies.Biomedicines · 2025Review
- The role of interleukin-17 in neurological disorders.Animal cells and systems · 2025Review
- Uncovering a new mechanism of ischemic stroke: a study of the association between γδ T cells and immunoinflammation.Frontiers in immunology · 2025Review
- Th17 Cells and IL-17A in Ischemic Stroke.Molecular neurobiology · 2024Review
- miR-154-5p Is a Novel Endogenous Ligand for TLR7 Inducing Microglial Activation and Neuronal Injury.Cells · 2024Article
- Interplay between Microbiota and γδ T Cells: Insights into Immune Homeostasis and Neuro-Immune Interactions.International journal of molecular sciences · 2024Review
- Increased Interleukin-17-Producing γδT Cells in the Brain Exacerbate the Pathogenesis of Sepsis-Associated Encephalopathy and Sepsis-Induced Anxiety in Mice.Journal of clinical medicine · 2023Article
- Role of microglia in HIV-1 infection.AIDS research and therapy · 2023Review
- Tissue-resident immune cells in the pathogenesis of multiple sclerosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Inflammatory Responses After Ischemic Stroke.Seminars in immunopathology · 2022Review
- CXCL13 expressed on inflamed cerebral blood vessels recruit IL-21 producing TJournal of neuroinflammation · 2022Article
- The role of Th17 cells/IL-17A in AD, PD, ALS and the strategic therapy targeting on IL-17A.Journal of neuroinflammation · 2022Review
- NPT1220-312, a TLR2/TLR9 Small Molecule Antagonist, Inhibits Pro-Inflammatory Signaling, Cytokine Release, and NLRP3 Inflammasome Activation.International journal of inflammation · 2022Article
- Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInterleukin-17 (IL-17) acts as a key regulator in central nervous system (CNS) inflammation. γδ T cells are an important innate source of IL-17. Both IL-17+ γδ T cells and microglia, the major resident immune cells of the brain, are involved in various CNS disorders such as multiple sclerosis and stroke. Also, activation of Toll-like receptor (TLR) signaling pathways contributes to CNS damage. However, the mechanisms underlying the regulation and interaction of these cellular and molecular components remain unclear.
objectiveIn this study, we investigated the crosstalk between γδ T cells and microglia activated by TLRs in the context of neuronal damage. To this end, co-cultures of IL-17+ γδ T cells, neurons, and microglia were analyzed by immunocytochemistry, flow cytometry, ELISA and multiplex immunoassays.
resultsWe report here that IL-17+ γδ T cells but not naïve γδ T cells induce a dose- and time-dependent decrease of neuronal viability in vitro. While direct stimulation of γδ T cells with various TLR ligands did not result in up-regulation of CD69, CD25, or in IL-17 secretion, supernatants of microglia stimulated by ligands specific for TLR2, TLR4, TLR7, or TLR9 induced activation of γδ T cells through IL-1β and IL-23, as indicated by up-regulation of CD69 and CD25 and by secretion of vast amounts of IL-17. This effect was dependent on the TLR adaptor myeloid differentiation primary response gene 88 (MyD88) expressed by both γδ T cells and microglia, but did not require the expression of TLRs by γδ T cells. Similarly to cytokine-primed IL-17+ γδ T cells, IL-17+ γδ T cells induced by supernatants derived from TLR-activated microglia also caused neurotoxicity in vitro. While these neurotoxic effects required stimulation of TLR2, TLR4, or TLR9 in microglia, neuronal injury mediated by bone marrow-derived macrophages did not require TLR signaling. Neurotoxicity mediated by IL-17+ γδ T cells required a direct cell-cell contact between T cells and neurons.
conclusionTaken together, these results point to a crucial role for microglia activated through TLRs in polarization of γδ T cells towards neurotoxic IL-17+ γδ T cells.
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