ArticleThe Journal of clinical investigation2013
A disease-associated PTPN22 variant promotes systemic autoimmunity in murine models.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 1 of them a synthesis that pooled it.
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Who cites it
118 citing papers in PubMed, 1 synthesis or guideline pooled it, 181 citations in OpenAlex.
- The Association between PTPN22 SNPs and susceptibility to type 1 diabetes: An updated meta-analysis.PloS one · 2025Pooled it
- Identifying Co-Expressed lncRNAs Correlated With Traits of Interest in an Animal Model for Metabolic Diseases in Humans.Animal genetics · 2026Article
- A Potent and Selective Quinolone-Based PTPN22 Inhibitor with Improved Immunotherapeutic Activity.Journal of medicinal chemistry · 2026Article
- An autoimmunity-associated allele ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Lyn governs the establishment and maintenance of B cell anergy by suppressing PI3K signaling.Nature communications · 2026Article
- The shared genetic architecture underlying the autoimmune and cardiovascular disease: a multivariate genome-wide analysis.Cardiovascular diabetology · 2026Article
- Type I interferon production in myeloid cells is regulated by factors independent of Ptpn22.ImmunoHorizons · 2025Article
- An Autoimmunity-associated allele ofbioRxiv : the preprint server for biology · 2025Article
- Towards a unifying model for B-cell receptor triggering.Nature reviews. Immunology · 2025Review
- Androgens contribute to sex bias of autoimmunity in mice by T cell-intrinsic regulation of Ptpn22 phosphatase expression.Nature communications · 2024Article
- NADPH oxidase exerts a B cell-intrinsic contribution to lupus risk by modulating endosomal TLR signals.The Journal of experimental medicine · 2024Article
- Autoimmunity-associated allele of tyrosine phosphatase gene PTPN22 enhances anti-viral immunity.PLoS pathogens · 2024Article
- Regulation of T Cell Signaling and Immune Responses by PTPN22.Molecular and cellular biology · 2024Review
- CARD19, a Novel Regulator of the TAK1/NF-κB Pathway in Self-Reactive B Cells.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Article
- Phenotypic and functional characteristics of murine CD11c+ B cells which is suppressed by metformin.Frontiers in immunology · 2023Article
- Genetic Polymorphism ofMedicina (Kaunas, Lithuania) · 2022Review
- PTPN22: structure, function, and developments in inhibitor discovery with applications for immunotherapy.Expert opinion on drug discovery · 2022Review
- Age-associated B cells in autoimmune diseases.Cellular and molecular life sciences : CMLS · 2022Review
- Regulation of activated T cell survival in rheumatic autoimmune diseases.Nature reviews. Rheumatology · 2022Review
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Multiple autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, Graves disease, and systemic lupus erythematosus, are associated with an allelic variant of protein tyrosine phosphatase nonreceptor 22 (PTPN22), which encodes the protein LYP. To model the human disease-linked variant LYP-R620W, we generated knockin mice expressing the analogous mutation, R619W, in the murine ortholog PEST domain phosphatase (PEP). In contrast with a previous report, we found that this variant exhibits normal protein stability, but significantly alters lymphocyte function. Aged knockin mice exhibited effector T cell expansion and transitional, germinal center, and age-related B cell expansion as well as the development of autoantibodies and systemic autoimmunity. Further, PEP-R619W affected B cell selection and B lineage-restricted variant expression and was sufficient to promote autoimmunity. Consistent with these features, PEP-R619W lymphocytes were hyperresponsive to antigen-receptor engagement with a distinct profile of tyrosine-phosphorylated substrates. Thus, PEP-R619W uniquely modulates T and B cell homeostasis, leading to a loss in tolerance and autoimmunity.
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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.