ArticleJCI insight2022
Monocyte proinflammatory phenotypic control by ephrin type A receptor 4 mediates neural tissue damage.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Gene expression and histological assessment of capsular fibrosis in post-traumatic shoulder stiffness following plate fixation of proximal humeral fractures: an exploratory pilot study.BMC musculoskeletal disorders · 2026Article
- Venezuelan equine encephalitis virus infection causes chronic neurobehavioral outcomes, cellular remodeling, and hippocampal single-cell transcriptomic changes.PLoS pathogens · 2026Article
- Hematopoietic EphA4 deficiency alters microglial heterogeneity and improves chronic spatial memory after brain injury.Scientific reports · 2025Article
- Eph Receptors Activate Myeloid Checkpoint Receptor LILRB5 to Support Tumor Development.Cancer immunology research · 2025Article
- Interrogating mediators of single-cell transcriptional changes in the acute damaged cerebral cortex: Insights into endothelial-astrocyte interactions.Molecular and cellular neurosciences · 2025Article
- Article
- Idebenone Enhances the Early Microglial Response to Traumatic Brain Injury and Mitigates Acute Gene Expression Changes to Ephrin-A and Dopamine Signaling Pathways.bioRxiv : the preprint server for biology · 2025Article
- Skull bone marrow-derived immune cells infiltrate the injured cerebral cortex and exhibit anti-inflammatory properties.Brain, behavior, and immunity · 2025Article
- Recent advances of the Ephrin and Eph family in cardiovascular development and pathologies.iScience · 2024Review
- Transcriptomic alterations in cortical astrocytes following the development of post-traumatic epilepsy.Scientific reports · 2024Article
- Immunoregulatory and neutrophil-like monocyte subsets with distinct single-cell transcriptomic signatures emerge following brain injury.Journal of neuroinflammation · 2024Article
- Lipidation and PEGylation Strategies to Prolong theEuropean journal of medicinal chemistry · 2023Article
- Efferocytosis is restricted by axon guidance molecule EphA4 via ERK/Stat6/MERTK signaling following brain injury.Journal of neuroinflammation · 2023Article
- Aging disrupts MANF-mediated immune modulation during skeletal muscle regeneration.Nature aging · 2023Article
- Article
- Cross-Talk and Subset Control of Microglia and Associated Myeloid Cells in Neurological Disorders.Cells · 2022Review
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
Circulating monocytes have emerged as key regulators of the neuroinflammatory milieu in a number of neuropathological disorders. Ephrin type A receptor 4 (Epha4) receptor tyrosine kinase, a prominent axon guidance molecule, has recently been implicated in the regulation of neuroinflammation. Using a mouse model of brain injury and a GFP BM chimeric approach, we found neuroprotection and a lack of significant motor deficits marked by reduced monocyte/macrophage cortical infiltration and an increased number of arginase-1+ cells in the absence of BM-derived Epha4. This was accompanied by a shift in monocyte gene profile from pro- to antiinflammatory that included increased Tek (Tie2 receptor) expression. Inhibition of Tie2 attenuated enhanced expression of M2-like genes in cultured Epha4-null monocytes/macrophages. In Epha4-BM-deficient mice, cortical-isolated GFP+ monocytes/macrophages displayed a phenotypic shift from a classical to an intermediate subtype, which displayed reduced Ly6chi concomitant with increased Ly6clo- and Tie2-expressing populations. Furthermore, clodronate liposome-mediated monocyte depletion mimicked these effects in WT mice but resulted in attenuation of phenotype in Epha4-BM-deficient mice. This demonstrates that monocyte polarization not overall recruitment dictates neural tissue damage. Thus, coordination of monocyte proinflammatory phenotypic state by Epha4 is a key regulatory step mediating brain injury.
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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.