ArticlePLoS biology2019
The interleukin-4/PPARγ signaling axis promotes oligodendrocyte differentiation and remyelination after brain injury.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 156 citations in OpenAlex.
- Nanodrugs for the Treatment of Ischemic Stroke: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Adiponectin Fortifies White Matter After Chronic Hypoperfusion-Induced Vascular Dementia.Stroke · 2026Article
- CTSS regulates macrophage lipid metabolic reprogramming and white matter repair after intracerebral hemorrhage.Journal of translational medicine · 2026Article
- Exercise mimetics: molecular mechanisms, biological and therapeutic effects.Molecular biomedicine · 2026Review
- Discovery and Characterization of Interleukin-4-Specific Affibodies for Affinity-Controlled Protein Release and Macrophage Polarization.bioRxiv : the preprint server for biology · 2026Article
- Single-cell transcriptomic analyses reveal angiogenic vascular responses to chronic cerebral hypoperfusion.iScience · 2026Article
- Endothelial cells temporally orchestrate lymphocyte dynamics and functional outcomes after ischemic stroke.Fluids and barriers of the CNS · 2026Article
- Neurons differentially upregulate type 2 immune cytokines and interleukin-4 receptor subtypes during neuroinflammation.Acta neuropathologica communications · 2026Article
- Neuroglia and immune cells play different roles in neuroinflammation and neuroimmune response in post-stroke neural injury and repair.Acta pharmacologica Sinica · 2026Review
- Monocyte-derived macrophages and their roles in ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Interleukin-4-Enhanced Oligodendrocyte Differentiation Depends on Extracellular Zinc Uptake via ZIP11.Cells · 2025Article
- Nanoparticle-Mediated Nose-to-Brain Delivery for Ischemic Stroke Therapy: Preclinical Insights.Pharmaceutics · 2025Review
- Development of a Human Preclinical Platform for the Identification of Neuroprotective Compounds.The European journal of neuroscience · 2025Article
- The application of telmisartan in central nervous system disorders.Pharmacological reports : PR · 2025Review
- Dihydroartemisinin enhances remyelination by switching microglia to the reparative phenotype.Journal of neuroinflammation · 2025Article
- Pro-repair macrophages driven by CGRP rescue white matter integrity following intracerebral hemorrhage.Journal of neuroinflammation · 2025Article
- RiboTag-based RNA profiling uncovers oligodendroglial lineage-specific inflammation in autoimmune encephalomyelitis: implications for pathogenesis.Journal of neuroinflammation · 2025Article
- Intermittent Fasting Enhances Motor Coordination Through Myelin Preservation in Aged Mice.Aging cell · 2025Article
- Argan Oil: A Natural Bioactive Lipid Modulating Oxidative Stress and Inflammation.Antioxidants (Basel, Switzerland) · 2025Review
- Repair-associated macrophages increase after early-phase microglia attenuation to promote ischemic stroke recovery.Nature communications · 2025Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
The repair of white matter damage is of paramount importance for functional recovery after brain injuries. Here, we report that interleukin-4 (IL-4) promotes oligodendrocyte regeneration and remyelination. IL-4 receptor expression was detected in a variety of glial cells after ischemic brain injury, including oligodendrocyte lineage cells. IL-4 deficiency in knockout mice resulted in greater deterioration of white matter over 14 d after stroke. Consistent with these findings, intranasal delivery of IL-4 nanoparticles after stroke improved white matter integrity and attenuated long-term sensorimotor and cognitive deficits in wild-type mice, as revealed by histological immunostaining, electron microscopy, diffusion tensor imaging, and electrophysiology. The selective effect of IL-4 on remyelination was verified in an ex vivo organotypic model of demyelination. By leveraging primary oligodendrocyte progenitor cells (OPCs), microglia-depleted mice, and conditional OPC-specific peroxisome proliferator-activated receptor gamma (PPARγ) knockout mice, we discovered a direct salutary effect of IL-4 on oligodendrocyte differentiation that was mediated by the PPARγ axis. Our findings reveal a new regenerative role of IL-4 in the central nervous system (CNS), which lies beyond its known immunoregulatory functions on microglia/macrophages or peripheral lymphocytes. Therefore, intranasal IL-4 delivery may represent a novel therapeutic strategy to improve white matter integrity in stroke and other brain injuries.
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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.