ArticleThe Journal of clinical investigation2011
T cell protein tyrosine phosphatase attenuates T cell signaling to maintain tolerance in mice.
Article in The Journal of clinical investigation, 2011. 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 128 papers, 2 of them syntheses that pooled it.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
128 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Association of PTPN22 SNP1858 (rs2476601) and Gene SNP1123 (rs2488457) Polymorphism With Primary Immune Thrombocytopenia Susceptibility: A Meta-Analysis of Case-Control Studies and Trial Sequential Analysis.Frontiers in genetics · 2022Pooled it
- Regulation of TCR signalling by tyrosine phosphatases: from immune homeostasis to autoimmunity.Immunology · 2012Pooled it
- Ptpn2 limits plasma cell fate and antiviral immunity by integrating B cell receptor and IFN-γ signals in B cells.Science advances · 2026Article
- Discovery of Noninhibitory Macrocyclic Ligands for Protein Tyrosine Phosphatase 1B Using a Function-Based, Iterative Screening Strategy.Journal of the American Chemical Society · 2026Article
- T cell lymphomas: cancers of aberrant immune synapse signalling.Nature reviews. Immunology · 2026Review
- Molecular Mechanisms and Targeted Therapies of PTPN2 in Metabolic Diseases: A Review.Biomolecules · 2026Review
- A Novel PTPN2 Isoform Differentially Regulates Immune Response.European journal of immunology · 2026Article
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- Deletion of Ptpn2 in B cells promotes autoimmunity via TLR and JAK/STAT signaling.JCI insight · 2025Article
- Recent advances in targeting protein degradation for tumor immunotherapy.Journal of hematology & oncology · 2025Review
- Uncovering the individual immunotherapeutic roles of PTPN1 and PTPN2 in T cells during dual inhibition.iScience · 2025Article
- The phosphatases TCPTP, PTPN22, and SHP1 play unique roles in T cell phosphotyrosine maintenance and feedback regulation of the TCR.Scientific reports · 2025Article
- Silencing PTPN2 with nanoparticle-delivered small interfering RNA remodels tumor microenvironment to sensitize immunotherapy in hepatocellular carcinoma.Acta pharmaceutica Sinica. B · 2025Article
- Circulating exo-miRNA-27a-5p is a novel biomarker of the tofacitinib treatment response in rheumatoid arthritis.BMC rheumatology · 2025Article
- Protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene polymorphisms (rs2542151, rs7234029) in Egyptian Behçet's disease patients: a preliminary report.Clinical rheumatology · 2024Article
- Protein tyrosine phosphatase non-receptor II: A possible biomarker of poor prognosis and mediator of immune evasion in hepatocellular carcinoma.World journal of gastrointestinal oncology · 2024Article
- Enhancing the apo protein tyrosine phosphatase non-receptor type 2 crystal soaking strategy through inhibitor-accessible binding sites.Acta crystallographica. Section F, Structural biology communications · 2024Article
- Development of Novel Phosphonodifluoromethyl-Containing Phosphotyrosine Mimetics and a First-In-Class, Potent, Selective, and Bioavailable Inhibitor of Human CDC14 Phosphatases.Journal of medicinal chemistry · 2024Article
- Protein tyrosine phosphatase 1B in metabolic diseases and drug development.Nature reviews. Endocrinology · 2024Review
- ABCD of IA: A multi-scale agent-based model of T cell activation in inflammatory arthritis.Biomaterials science · 2024Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many autoimmune diseases exhibit familial aggregation, indicating that they have genetic determinants. Single nucleotide polymorphisms in PTPN2, which encodes T cell protein tyrosine phosphatase (TCPTP), have been linked with the development of several autoimmune diseases, including type 1 diabetes and Crohn's disease. In this study, we have identified TCPTP as a key negative regulator of TCR signaling, which might explain the association of PTPN2 SNPs with autoimmune disease. We found that TCPTP dephosphorylates and inactivates Src family kinases to regulate T cell responses. Using T cell-specific TCPTP-deficient mice, we established that TCPTP attenuates T cell activation and proliferation in vitro and blunts antigen-induced responses in vivo. TCPTP deficiency lowered the in vivo threshold for TCR-dependent CD8(+) T cell proliferation. Consistent with this, T cell-specific TCPTP-deficient mice developed widespread inflammation and autoimmunity that was transferable to wild-type recipient mice by CD8(+) T cells alone. This autoimmunity was associated with increased serum levels of proinflammatory cytokines and anti-nuclear antibodies, T cell infiltrates in non-lymphoid tissues, and liver disease. These data indicate that TCPTP is a critical negative regulator of TCR signaling that sets the threshold for TCR-induced naive T cell responses to prevent autoimmune and inflammatory disorders arising.
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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.