ArticleJournal of immunology (Baltimore, Md. : 1950)2009
PTPN22 deficiency cooperates with the CD45 E613R allele to break tolerance on a non-autoimmune background.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 5 of them syntheses that pooled it.
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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.
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Who cites it
84 citing papers in PubMed, 5 syntheses or guidelines pooled it, 126 citations in OpenAlex.
- 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
- The association between rs2476601 polymorphism in PTPN22 gene and risk of alopecia areata: A meta-analysis of case-control studies.Medicine · 2019Pooled it
- PTPN22 R620W Polymorphism is Associated with Myasthenia Gravis Risk: A Systematic Review and Meta-Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2015Pooled it
- Regulation of TCR signalling by tyrosine phosphatases: from immune homeostasis to autoimmunity.Immunology · 2012Pooled it
- Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis.Annals of the rheumatic diseases · 2011Pooled it
- Exploring the comorbidity mechanisms between atherosclerosis and hashimoto's thyroiditis based on microarray and single-cell sequencing analysis.Scientific reports · 2025Article
- Regulation of T Cell Signaling and Immune Responses by PTPN22.Molecular and cellular biology · 2024Review
- Article
- The unequal functional redundancy of ArabidopsisFrontiers in plant science · 2023Article
- PTPN22: structure, function, and developments in inhibitor discovery with applications for immunotherapy.Expert opinion on drug discovery · 2022Review
- Polygenic autoimmune disease risk alleles impacting B cell tolerance act in concert across shared molecular networks in mouse and in humans.Frontiers in immunology · 2022Review
- Overexpression of theJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- Influence ofFrontiers in immunology · 2021Review
- Autoimmunity linked protein phosphatase PTPN22 as a target for cancer immunotherapy.Journal for immunotherapy of cancer · 2020Article
- Association of Functional Polymorphism in Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) Gene with Vitiligo.Biomarker insights · 2020Article
- Efficient CRISPR/Cas9 Disruption of Autoimmune-Associated Genes Reveals Key Signaling Programs in Primary Human T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Whole exome sequencing in childhood-onset lupus frequently detects single gene etiologies.Pediatric rheumatology online journal · 2019Article
- PTPN22 1858C>T polymorphism is associated with increased CD154 expression and higher CD4+ T cells percentage in rheumatoid arthritis patients.Journal of clinical laboratory analysis · 2019Article
- Regulation of autoimmune and anti-tumour T-cell responses by PTPN22.Immunology · 2018Review
- Protein Tyrosine Phosphatases: Regulators of CD4 T Cells in Inflammatory Bowel Disease.Frontiers in immunology · 2018Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Pep and CD45 are tyrosine phosphatases whose targets include the Src-family kinases, critical mediators of Ag receptor signaling. A polymorphism in PTPN22, the gene that encodes the human Pep orthologue Lyp, confers susceptibility to multiple human autoimmune diseases in the context of complex genetic backgrounds. However, the functional significance of the R620W risk allele is not clear. We report that misexpression of wild-type or R620W Pep/Lyp in Jurkat cells, in the context of its binding partner Csk, unmasks the risk allele as a hypomorph. It has been shown previously that although Pep-deficient mice on the B6 background have hyperresponsive memory T cells, autoimmunity does not develop. Mice containing a point mutation in the CD45 juxtamembrane wedge domain (E613R) develop a B cell-driven, lupus-like disease on the mixed 129/B6 background, but not on the B6 background. We studied the ability of Pep deficiency to act as a genetic modifier of the CD45 E613R mutation on the nonautoimmune B6 background to understand how complex susceptibility loci might interact in autoimmunity. In this study we report that double mutant mice develop a lupus-like disease as well as lymphadenopathy, polyclonal lymphocyte activation, and accelerated memory T cell formation. Following Ag receptor stimulation, peripheral B cells in the double mutant mice phenocopy hyperresponsive CD45 E613R B cells, whereas peripheral T cells respond like Pep(-/-) T cells. These studies suggest that Pep(-/-) T cells in the context of a susceptible microenvironment can drive hyperresponsive CD45 E613R B cells to break tolerance.
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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.