ArticleLaboratory investigation; a journal of technical methods and pathology2008
SHP-1 deficiency and increased inflammatory gene expression in PBMCs of multiple sclerosis patients.
Article in Laboratory investigation; a journal of technical methods and pathology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 61 citations in OpenAlex.
- Quantitative differences in the immunomodulatory effects of Rebif and Avonex in IFN-β 1a treated multiple sclerosis patients.Journal of the neurological sciences · 2011Trial
- Biallelic loss-of-function PTPN6 variants lead to inflammatory lung disease and hemolytic anemia.The Journal of experimental medicine · 2026Article
- Loss of SHP1 in Spinal Astrocytes Triggers T-Lymphocyte Infiltration and Nociceptive Hypersensitivity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PTPN1/PTPN2 inhibition improves NK cancer therapy by enhancing IL-2 and mitigating TGFβ1 responses.EMBO reports · 2026Article
- PTPN6/SHP-1 in autoimmune disease: immune tolerance, regulatory mechanisms, and therapeutic targeting.Frontiers in immunology · 2026Review
- The phosphatases TCPTP, PTPN22, and SHP1 play unique roles in T cell phosphotyrosine maintenance and feedback regulation of the TCR.Scientific reports · 2025Article
- Protein phosphatases in systemic autoimmunity.Immunometabolism (Cobham, Surrey) · 2025Review
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- Treg-specific deletion of the phosphatase SHP-1 impairs control of inflammationFrontiers in immunology · 2023Article
- Ets-2 deletion in myeloid cells attenuates IL-1α-mediated inflammatory disease caused by a Ptpn6 point mutation.Cellular & molecular immunology · 2021Article
- Differential expression of genes involved in the acute innate immune response to intracortical microelectrodes.Acta biomaterialia · 2020Article
- Modulation of TCR Signaling by Tyrosine Phosphatases: From Autoimmunity to Immunotherapy.Frontiers in cell and developmental biology · 2020Review
- Article
- Non-receptor tyrosine kinase signaling in autoimmunity and therapeutic implications.Pharmacology & therapeutics · 2019Review
- A Precision B Cell-Targeted Therapeutic Approach to Autoimmunity Caused by Phosphatidylinositol 3-Kinase Pathway Dysregulation.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Targeted SHP-1 Silencing Modulates the Macrophage Phenotype, Leading to Metabolic Improvement in Dietary Obese Mice.Molecular therapy. Nucleic acids · 2019Article
- Mechanisms of Inflammation in Neutrophil-Mediated Skin Diseases.Frontiers in immunology · 2019Review
- Cutting Edge: Dysregulated CARD9 Signaling in Neutrophils Drives Inflammation in a Mouse Model of Neutrophilic Dermatoses.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- ASK1/2 signaling promotes inflammation in a mouse model of neutrophilic dermatosis.The Journal of clinical investigation · 2018Article
- Putting on the Brakes: Regulatory Kinases and Phosphatases Maintaining B Cell Anergy.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Recent studies in mice have demonstrated that the protein tyrosine phosphatase SHP-1 is a crucial negative regulator of cytokine signaling, inflammatory gene expression, and demyelination in central nervous system. The present study investigates a possible similar role for SHP-1 in the human disease multiple sclerosis (MS). The levels of SHP-1 protein and mRNA in PBMCs of MS patients were significantly lower compared to normal subjects. Moreover, promoter II transcripts, expressed from one of two known promoters, were selectively deficient in MS patients. To examine functional consequences of the lower SHP-1 in PBMCs of MS patients, we measured the intracellular levels of phosphorylated STAT6 (pSTAT6). As expected, MS patients had significantly higher levels of pSTAT6. Accordingly, siRNA to SHP-1 effectively increased the levels of pSTAT6 in PBMCs of controls to levels equal to MS patients. Additionally, transduction of PBMCs with a lentiviral vector expressing SHP-1 lowered pSTAT6 levels. Finally, multiple STAT6-responsive inflammatory genes were increased in PBMCs of MS patients relative to PBMCs of normal subjects. Thus, PBMCs of MS patients display a stable deficiency of SHP-1 expression, heightened STAT6 phosphorylation, and an enhanced state of activation relevant to the mechanisms of inflammatory demyelination.
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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.