ArticleThe Journal of clinical investigation2015
MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 112 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
112 citing papers in PubMed, 199 citations in OpenAlex.
- Increased inflammatory cytokines in the temporal cortex in autism spectrum disorder.Brain, behavior, & immunity - health · 2026Article
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- IL-4 in Alzheimer's Disease-Mechanisms and Therapeutic Potential.Molecular neurobiology · 2026Review
- Differential brain neuroimmune profiles and altered immune balance in autism spectrum disorder compared with psychotic disorder and neurotypical controls.Research square · 2026Article
- Engineering chimeric antigen receptor CD4 T cells for Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Neurons differentially upregulate type 2 immune cytokines and interleukin-4 receptor subtypes during neuroinflammation.Acta neuropathologica communications · 2026Article
- Nested ecosystems theory for conceptualizing brain tumors.Disease models & mechanisms · 2026Review
- Systemic Interleukin-4 Application Promotes Functional Recovery and Reprograms Neuroinflammatory and Molecular Responses after Spinal Cord Injury in Rats.Theranostics · 2026Article
- Connection and communication between the nervous and immune systems.Nature reviews. Immunology · 2025Review
- Review
- Biomaterial-Based Emergency Intervention for Secondary Spinal Cord Injury.Small science · 2025Review
- Review
- Hypercholesterolemia Duration and Brain Area Determine Inflammatory Response Intensity and Apoptotic Mediator Activation in Apo ECellular and molecular neurobiology · 2025Article
- Understanding the pro- & anti-inflammatory cytokine profile in Japanese encephalitis & their implications in survival outcome.The Indian journal of medical research · 2025Article
- CD4Frontiers in immunology · 2025Review
- Neuroinflammation and acute ischemic stroke: impact on translational research and clinical care.Frontiers in surgery · 2025Review
- Bioactive hydrogel synergizes neuroprotection, macrophage polarization, and angiogenesis to improve repair of traumatic brain injury.Materials today. Bio · 2024Article
- 'Comprehensive review of emerging drug targets in traumatic brain injury (TBI): challenges and future scope.Inflammopharmacology · 2024Review
- Emerging Roles of Adaptive Immune Response in Alzheimer's Disease.Aging and disease · 2024Review
- Will cellular immunotherapies end neurodegenerative diseases?Trends in immunology · 2024Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
22 authors at 4 institutions in 3 countries.
Funding
Abstract
A body of experimental evidence suggests that T cells mediate neuroprotection following CNS injury; however, the antigen specificity of these T cells and how they mediate neuroprotection are unknown. Here, we have provided evidence that T cell-mediated neuroprotection after CNS injury can occur independently of major histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using two murine models of CNS injury, we determined that damage-associated molecular mediators that originate from injured CNS tissue induce a population of neuroprotective, IL-4-producing T cells in an antigen-independent fashion. Compared with wild-type mice, IL-4-deficient animals had decreased functional recovery following CNS injury; however, transfer of CD4+ T cells from wild-type mice, but not from IL-4-deficient mice, enhanced neuronal survival. Using a culture-based system, we determined that T cell-derived IL-4 protects and induces recovery of injured neurons by activation of neuronal IL-4 receptors, which potentiated neurotrophin signaling via the AKT and MAPK pathways. Together, these findings demonstrate that damage-associated molecules from the injured CNS induce a neuroprotective T cell response that is independent of MHCII/TCR interactions and is MyD88 dependent. Moreover, our results indicate that IL-4 mediates neuroprotection and recovery of the injured CNS and suggest that strategies to enhance IL-4-producing CD4+ T cells have potential to attenuate axonal damage in the course of CNS injury in trauma, inflammation, or neurodegeneration.
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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.