ArticleJCI insight2019
Deficiency of Socs3 leads to brain-targeted EAE via enhanced neutrophil activation and ROS production.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 56 citations in OpenAlex.
- Single-cell transcriptomic unveils tumor-mediated reprogramming of neutrophils and their unique vulnerability that inhibits metastasis.Science advances · 2026Article
- Single-cell RNA sequencing uncovers neutrophil clusters associated with autoimmune neuroinflammation.Journal of neuroinflammation · 2026Article
- Aging changes the mechanism that underlies JAK2 modulation of neutrophil function.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Regulation and Interaction Among SOCS1 and SOCS3 by MicroRNAs in Multiple Sclerosis: A Review andThe Yale journal of biology and medicine · 2026Review
- Single-Cell RNA Sequencing Uncovers Neutrophil Clusters Associated with Autoimmune Neuroinflammation.Research square · 2025Article
- SOCS3: An Immunological Biomarker Offering Potential Therapeutic Targets for Malignant Tumors.Biological procedures online · 2025Review
- Neutrophils, NETs and multiple sclerosis: a mini review.Frontiers in immunology · 2025Review
- Loss of Cullin 5 in myeloid cells protects against autoimmune neuroinflammation.Frontiers in immunology · 2025Article
- Analysis of CNS autoimmunity in genetically diverse mice reveals unique phenotypes and mechanisms.JCI insight · 2024Article
- Suppression of the JAK/STAT pathway inhibits neuroinflammation in the line 61-PFF mouse model of Parkinson's disease.Journal of neuroinflammation · 2024Article
- Single-Cell RNA Sequencing Reveals Transcriptional Landscape of Neutrophils and Highlights the Role of TREM-1 in EAE.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- Neurosteroid [3α,5α]-3-Hydroxy-pregnan-20-one Enhances the CX3CL1-CX3CR1 Pathway in the Brain of Alcohol-Preferring Rats with Sex-Specificity.Life (Basel, Switzerland) · 2024Article
- Suppression of the JAK/STAT Pathway Inhibits Neuroinflammation in the Line 61-PFF Mouse Model of Parkinson's Disease.Research square · 2024Article
- CSF1R antagonism results in increased supraspinal infiltration in EAE.Journal of neuroinflammation · 2024Article
- NLRP3 exacerbates EAE severity through ROS-dependent NET formation in the mouse brain.Cell communication and signaling : CCS · 2024Article
- Mitochondrial and metabolic dysfunction of peripheral immune cells in multiple sclerosis.Journal of neuroinflammation · 2024Review
- Diverse bacteria elicit distinct neutrophil responses in a physiologically relevant model of infection.iScience · 2024Article
- TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization.Neuroscience bulletin · 2024Article
- Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts.Nature communications · 2023Article
- Roles and regulation of microglia activity in multiple sclerosis: insights from animal models.Nature reviews. Neuroscience · 2023Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Dysregulation of the JAK/STAT signaling pathway is associated with Multiple Sclerosis (MS) and its mouse model, Experimental Autoimmune Encephalomyelitis (EAE). Suppressors Of Cytokine Signaling (SOCS) negatively regulate the JAK/STAT pathway. We previously reported a severe, brain-targeted, atypical form of EAE in mice lacking Socs3 in myeloid cells (Socs3ΔLysM), which is associated with cerebellar neutrophil infiltration. There is emerging evidence that neutrophils are detrimental in the pathology of MS/EAE, however, their exact function is unclear. Here we demonstrate that neutrophils from the cerebellum of Socs3ΔLysM mice show a hyper-activated phenotype with excessive production of reactive oxygen species (ROS) at the peak of EAE. Neutralization of ROS in vivo delayed the onset and reduced severity of atypical EAE. Mechanistically, Socs3-deficient neutrophils exhibit enhanced STAT3 activation, a hyper-activated phenotype in response to G-CSF, and upon G-CSF priming, increased ROS production. Neutralization of G-CSF in vivo significantly reduced the incidence and severity of the atypical EAE phenotype. Overall, our work elucidates that hypersensitivity of G-CSF/STAT3 signaling in Socs3ΔLysM mice leads to atypical EAE by enhanced neutrophil activation and increased oxidative stress, which may explain the detrimental role of G-CSF in MS patients.
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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.