ArticleThe Journal of clinical investigation2023
A20 regulates lymphocyte adhesion in murine neuroinflammation by restricting endothelial ICOSL expression in the CNS.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 11 citations in OpenAlex.
- The ubiquitin-editing enzyme A20 (TNFAIP3): mechanisms of activation, biological function, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Senescent Human Liver Endothelial Cells Mediate CD4Immunology · 2026Article
- The immune-endothelial axis in neurovascular pathophysiology: a framework for targeted interventions.Frontiers in immunology · 2026Review
- Global trends and mechanistic insights into A20 (TNFAIP3) in autoimmunity and inflammation.American journal of translational research · 2026Review
- Prognostic Nutritional Index as a Novel Biomarker for Predicting Prognosis in Sepsis-Associated Encephalopathy: A Multicenter Retrospective Cohort Study.Emergency medicine international · 2026Article
- Deubiquitinating enzymes at the crossroads of blood-brain barrier integrity and neurodegeneration: mechanistic insights, therapeutic targeting and future directions.Tissue barriers · 2026Review
- Health risk analysis of micro-and nanoplastic exposure via the microbiota-gut-brain axis.Frontiers in immunology · 2026Review
- Sphingolipid-Neuroinflammation Axis in Parkinson's Disease: Focus on S1P/SPHK1-NF‑κB Signaling.Journal of inflammation research · 2026Review
- Inflammation associated microglial expansion disrupts hippocampal glial network communication, driving postoperative neurocognitive impairment.Journal of neuroinflammation · 2025Article
- Integrating Microorganism-Based Therapy and Emerging Biotechnology in the Treatment of Intracranial Central Nervous System Diseases.Pharmaceutics · 2025Review
- Impact of Peripheral Inflammation on Blood-Brain Barrier Dysfunction and Its Role in Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Inflammatory Biomarkers in Coronary Artery Disease: Insights From Mendelian Randomization and Transcriptomics.Journal of inflammation research · 2025Article
- TNFAIP3 alleviates cerebral ischemia-reperfusion injury by inhibiting M1 microglia polarization via deubiquitination of RACK1.PloS one · 2025Article
- A20 negatively regulates necroptosis-induced microglia/macrophages polarization and mediates cerebral ischemic tolerance via inhibiting the ubiquitination of RIP3.Cell death & disease · 2024Article
- Evaluation of BR1 and BI30 AAVs for Brain Endothelial Tropism.ASN neuro · 2024Article
Corrections and comments
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Authors and funding
22 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A20 is a ubiquitin-modifying protein that negatively regulates NF-κB signaling. Mutations in A20/TNFAIP3 are associated with a variety of autoimmune diseases, including multiple sclerosis (MS). We found that deletion of A20 in central nervous system (CNS) endothelial cells (ECs) enhances experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. A20ΔCNS-EC mice showed increased numbers of CNS-infiltrating immune cells during neuroinflammation and in the steady state. While the integrity of the blood-brain barrier (BBB) was not impaired, we observed a strong activation of CNS-ECs in these mice, with dramatically increased levels of the adhesion molecules ICAM-1 and VCAM-1. We discovered ICOSL to be expressed by A20-deficient CNS-ECs, which we found to function as adhesion molecules. Silencing of ICOSL in CNS microvascular ECs partly reversed the phenotype of A20ΔCNS-EC mice without reaching statistical significance and delayed the onset of EAE symptoms in WT mice. In addition, blocking of ICOSL on primary mouse brain microvascular ECs impaired the adhesion of T cells in vitro. Taken together, we propose that CNS EC-ICOSL contributes to the firm adhesion of T cells to the BBB, promoting their entry into the CNS and eventually driving neuroinflammation.
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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.