ArticleThe Journal of clinical investigation2020
Astrocyte-microglia interaction drives evolving neuromyelitis optica lesion.
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 107 papers.
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Who cites it
107 citing papers in PubMed.
- Role of complement and complement-targeted therapeutics in neurological diseases.Nature reviews. Neurology · 2026Review
- ACSL4-mediated astrocyte ferroptosis augments neuroinflammation and exacerbates NMOSD pathology.Cell death and differentiation · 2026Article
- Targeting C3aR/STAT3 signaling attenuates neuroinflammation and reverses neurological impairment in Neuromyelitis optica.Fundamental research · 2026Article
- Article
- Dynamic characterization of pathological and functional deterioration in a mouse model of optic neuritis related to neuromyelitis optica spectrum disorder.Neural regeneration research · 2026Article
- Ferritin-ApoE nanocarrier for targeted therapy of neuromyelitis optica spectrum disorder in mice.Journal of neuroinflammation · 2026Article
- Astrocyte-to-microglia purinergic signaling mediates synaptic shielding and promotes neuronal activity.bioRxiv : the preprint server for biology · 2026Article
- Glial cells in chronic inflammation: diversity, dysfunction and therapeutic targeting.Nature reviews. Immunology · 2026Review
- Endothelial cell-secreted SPARC suppresses astrocytic CD59 expression and promotes astrocytopathy in a mouse model of neuromyelitis optica spectrum disorders.Nature communications · 2026Article
- Curing the brain: in search for new astrocyte-specific therapies.Experimental & molecular medicine · 2026Review
- Neutrophil-microglia interaction drives motor dysfunction in a neuromyelitis optica model induced by subarachnoid AQP4-IgG.The Journal of clinical investigation · 2026Article
- Natalizumab exacerbates astrocytopathy in NMOSD via blockade of endothelial VCAM1-astrocytic integrin α4 interaction.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Role of serum complement C3 in blood-brain barrier injury and prognosis of anti-NMDAR encephalitis.BMC neurology · 2026Article
- AQP4-IgG-Induced Astrocyte-Derived Small Extracellular Vesicles Carrying Mitochondrial DNA Regulate the TLR9/MyD88/NF-κB Pathway to Drive Microglial Activation and Neuromyelitis Optica.Neurochemical research · 2026Article
- Review
- Aquaporin-4 deficiency induced white matter injury via upregulated complement component 3 in cerebral small vessel disease.Journal of neuroinflammation · 2026Article
- The Role of the C3a-C3aR Pathway in Diseases: Latest Research Advances.Mediators of inflammation · 2026Review
- CXCL9 associates with experimental neuromyelitis optica spectrum disorder following adoptive transfer of Tfh and Th17 cells.Frontiers in immunology · 2026Article
- Microglial Rack1 Deficiency Alleviates Alzheimer's Disease Pathology through Enhancing IGF1-Mediated Astrocytic Phagocytosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Why repair fails in AQP4-IgG-positive neuromyelitis optica spectrum disease: an astrocyte-centered framework for remyelination and neuroaxonal preservation.Frontiers in immunology · 2026Review
47 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
Abstract
Neuromyelitis optica (NMO) is a severe inflammatory autoimmune CNS disorder triggered by binding of an IgG autoantibody to the aquaporin 4 (AQP4) water channel on astrocytes. Activation of cytolytic complement has been implicated as the major effector of tissue destruction that secondarily involves myelin. We investigated early precytolytic events in the evolving pathophysiology of NMO in mice by continuously infusing IgG (NMO patient serum-derived or AQP4-specific mouse monoclonal), without exogenous complement, into the spinal subarachnoid space. Motor impairment and sublytic NMO-compatible immunopathology were IgG dose dependent, AQP4 dependent, and, unexpectedly, microglia dependent. In vivo spinal cord imaging revealed a striking physical interaction between microglia and astrocytes that required signaling from astrocytes by the C3a fragment of their upregulated complement C3 protein. Astrocytes remained viable but lost AQP4. Previously unappreciated crosstalk between astrocytes and microglia involving early-activated CNS-intrinsic complement components and microglial C3a receptor signaling appears to be a critical driver of the precytolytic phase in the evolving NMO lesion, including initial motor impairment. Our results indicate that microglia merit consideration as a potential target for NMO therapeutic intervention.
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