ArticleJournal of neuroinflammation2018
Aberrant STAT phosphorylation signaling in peripheral blood mononuclear cells from multiple sclerosis patients.
Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- The Role of Interferon-α in Neurodegenerative Diseases: A Systematic Review.Journal of Alzheimer's disease : JAD · 2023Pooled it
- Targeting pyruvate kinase M2 (PKM2) reduces T cell pathogenicity in multiple sclerosis.EBioMedicine · 2026Article
- Elevated TNF-α level is correlated with NF-κB/p65 activation in patients with sporadic colorectal cancer.Molecular and clinical oncology · 2026Article
- Single-cell RNA sequencing uncovers neutrophil clusters associated with autoimmune neuroinflammation.Journal of neuroinflammation · 2026Article
- Role of CD5 signalling for pro-inflammatory Th17 response in multiple sclerosis.Brain : a journal of neurology · 2026Article
- Neuroinflammation and Disease: Pathways and Opportunities.Annual review of pharmacology and toxicology · 2026Review
- Single-Cell RNA Sequencing Uncovers Neutrophil Clusters Associated with Autoimmune Neuroinflammation.Research square · 2025Article
- The search for a blood-based biomarker for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): from biochemistry to electrophysiology.Journal of translational medicine · 2025Review
- Diverse signaling mechanisms and heterogeneity of astrocyte reactivity in Alzheimer's disease.Journal of neurochemistry · 2024Review
- Obesity intensifies sex-specific interferon signaling to selectively worsen central nervous system autoimmunity in females.Cell metabolism · 2024Article
- Phosphoflow cytometry to assess cytokine signaling pathways in peripheral immune cells: potential for inferring immune cell function and treatment response in patients with solid tumors.Journal of experimental & clinical cancer research : CR · 2023Review
- Simultaneous Assessment of mTORC1, JAK/STAT, and NLRP3 Inflammasome Activation Pathways in Patients with Sarcoidosis.International journal of molecular sciences · 2023Article
- High-dimensional immune profiling identifies a biomarker to monitor dimethyl fumarate response in multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Role of JAK-STAT and PPAR-Gamma Signalling Modulators in the Prevention of Autism and Neurological Dysfunctions.Molecular neurobiology · 2022Review
- Effect of puberty on the immune system: Relevance to multiple sclerosis.Frontiers in pediatrics · 2022Review
- Prediction of combination therapies based on topological modeling of the immune signaling network in multiple sclerosis.Genome medicine · 2021Article
- Article
- A splice acceptor variant in HLA-DRA affects the conformation and cellular localization of the class II DR alpha-chain.Immunology · 2021Article
- Cytokines and Transgenic Matrix in Autoimmune Diseases: Similarities and Differences.Biomedicines · 2020Review
- STAT3 signaling in myeloid cells promotes pathogenic myelin-specific T cell differentiation and autoimmune demyelination.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMultiple sclerosis (MS) is characterized by increased activation of peripheral blood mononuclear cells (PBMCs), linked to perturbations in the phosphorylation of signaling proteins.
methodsWe developed a phosphoflow cytometry protocol to assess the levels of 11 phosphorylated nuclear proteins at baseline conditions and after cell activation in distinct PBMC populations from 41 treatment-naïve relapsing-remitting (RR) MS subjects and 37 healthy controls, and in a second cohort of 9 untreated RRMS patients and 10 secondary progressive (SP) MS patients. Levels of HLA-ABC, HLA-E, and HLA-DR were also assessed. Phosphorylation levels of selected proteins were also assessed in mouse splenocytes isolated from myelin oligodendrocyte glycoprotein (MOG)
resultsModest differences were observed at baseline between patients and controls, with general lower phosphorylation levels in cells from affected individuals. Conversely, a dramatic increase in phosphorylated p38MAPK and STAT proteins was observed across all cell types in MS patients compared to controls after in vitro activation. A similar phosphorylation profile was observed in mouse lymphocytes primed in vivo with MOG. Furthermore, levels of all p-STAT proteins were found directly correlated with HLA expression in monocytes. Levels of phosphorylated proteins did not differ between relapsing-remitting and secondary progressive MS patients either in baseline conditions or after stimulation. Lastly, phosphorylation levels appear to be independent of the genotype.
conclusionThe response to IFN-α through STAT proteins signaling is strongly dysregulated in MS patients irrespective of disease stage. These findings suggest that the aberrant activation of this pathway could lead to changes in the expression of HLA molecules in antigen presenting cells, which are known to play important roles in the regulation of the immune response in health and disease.
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Registered trials
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