ArticleCellular and molecular life sciences : CMLS2021
Polysialic acid and Siglec-E orchestrate negative feedback regulation of microglia activation.
Article in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Microglia and neuroinflammation: An in-depth analysis from functional diversity to disease mechanisms.Clinical and translational medicine · 2026Review
- Mesenchymal WNT signaling coordinates epithelial and mesenchymal differentiation in the developing murine ureter.Cell communication and signaling : CCS · 2026Article
- In planta engineering of polysialylated glycoproteins using salmonid polysialyltransferases.Scientific reports · 2026Article
- Sialylation in the nervous system: Functions and mechanisms.The Journal of biological chemistry · 2026Review
- Nanoparticle Delivery Systems in Rheumatoid Arthritis: More Than Vehicles.Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026Review
- Loss of ST8Sia6 mediated α-2,8-linked di-sialylation enhances T cell-dependent antibody responses and promotes autoimmunity in aged mice.Frontiers in immunology · 2026Article
- Polysialic acid is upregulated on activated immune cells and negatively regulates anticancer immune activity.Frontiers in oncology · 2025Article
- CD22 blockade aggravates EAE and its role in microglia polarization.CNS neuroscience & therapeutics · 2024Article
- Siglec-E Ligand Downregulation on Hippocampus Neurons Induced Inflammation in Sevoflurane-Associated Perioperative Neurocognitive Disorders in Aged Mice.Inflammation · 2024Article
- Sialic Acid Mimetic Microglial Sialic Acid-Binding Immunoglobulin-like Lectin Agonism: Potential to Restore Retinal Homeostasis and Regain Visual Function in Age-Related Macular Degeneration.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Polysialylation controls immune function of myeloid cells in murine model of pneumococcal pneumonia.Cell reports · 2023Article
- Proinflammatory Macrophage Activation by the Polysialic Acid-Siglec-16 Axis Is Linked to Increased Survival of Patients with Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Neuroimmunomodulatory properties of polysialic acid.Glycoconjugate journal · 2023Review
- Association of polysialic acid serum levels with schizophrenia spectrum and bipolar disorder-related structural brain changes and hospitalization.Scientific reports · 2023Article
- Polysialic acid promotes remyelination in cerebellar slice cultures by Siglec-E-dependent modulation of microglia polarization.Frontiers in cellular neuroscience · 2023Article
- PolySialic acid-nanoparticles inhibit macrophage mediated inflammation through Siglec agonism: a potential treatment for age related macular degeneration.Frontiers in immunology · 2023Article
- Article
- Polysialic Acid Sustains the Hypoxia-Induced Migration and Undifferentiated State of Human Glioblastoma Cells.International journal of molecular sciences · 2022Article
- GATA6 is a crucial factor for Myocd expression in the visceral smooth muscle cell differentiation program of the murine ureter.Development (Cambridge, England) · 2022Article
- Ablation of Siglec-E augments brain inflammation and ischemic injury.Journal of neuroinflammation · 2022Article
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3 authors.
Funding
Abstract
Polysialic acid (polySia) emerges as a novel regulator of microglia activity. We recently identified polysialylated proteins in the Golgi compartment of murine microglia that are released in response to inflammatory stimulation. Since exogenously added polySia is able to attenuate the inflammatory response, we proposed that the release of polysialylated proteins constitutes a mechanism for negative feedback regulation of microglia activation. Here, we demonstrate that translocation of polySia from the Golgi to the cell surface can be induced by calcium depletion of the Golgi compartment and that polysialylated proteins are continuously released for at least 24 h after the onset of inflammatory stimulation. The latter was unexpected, because polySia signals detected by immunocytochemistry are rapidly depleted. However, it indicates that the amount of released polySia is much higher than anticipated based on immunostaining. This may be crucial for microglial responses during traumatic brain injury (TBI), as we detected polySia signals in activated microglia around a stab wound in the adult mouse brain. In BV2 microglia, the putative polySia receptor Siglec-E is internalized during lipopolysaccharide (LPS)-induced activation and in response to polySia exposure, indicating interaction. Correspondingly, CRISPR/Cas9-mediated Siglec-E knockout prevents inhibition of pro inflammatory activation by exogenously added polySia and leads to a strong increase of the LPS response. A comparable increase of LPS-induced activation has been observed in microglia with abolished polySia synthesis. Together, these results indicate that the release of the microglia-intrinsic polySia pool, as implicated in TBI, inhibits the inflammatory response by acting as a trans-activating ligand of Siglec-E.
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