ArticlePloS one2014
Autoimmunity-associated LYP-W620 does not impair thymic negative selection of autoreactive T cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- PTPN22-CD45 dual phosphatase retrograde feedback enhances TCR signaling and autoimmunity.Science advances · 2025Article
- Clinical value of the expression levels of protein tyrosine phosphatase non-receptor type 22.6 mRNA in peripheral blood mononuclear cells in Crohn's disease.Clinical and experimental immunology · 2022Article
- Regulation of autoimmune and anti-tumour T-cell responses by PTPN22.Immunology · 2018Review
- The PTPN22 R263Q polymorphism confers protection against systemic lupus erythematosus and rheumatoid arthritis, while PTPN22 R620W confers susceptibility to Graves' disease in a Mexican population.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2017Article
- PTPN22 and islet-specific autoimmunity: What have the mouse models taught us?World journal of diabetes · 2017Review
- Use of short interfering RNA delivered by cationic liposomes to enable efficient down-regulation of PTPN22 gene in human T lymphocytes.PloS one · 2017Article
- The functional PTPN22 C1858T polymorphism confers risk for rheumatoid arthritis in patients from Central Mexico.Clinical rheumatology · 2016Article
- The genetics of rheumatoid arthritis: risk and protection in different stages of the evolution of RA.Rheumatology (Oxford, England) · 2016Review
- The genetics of human autoimmune disease: A perspective on progress in the field and future directions.Journal of autoimmunity · 2015Review
- Lack of the protein tyrosine phosphatase PTPN22 strengthens transplant tolerance to pancreatic islets in mice.Diabetologia · 2015Article
- The role of PTPN22 risk variant in the development of autoimmunity: finding common ground between mouse and human.Journal of immunology (Baltimore, Md. : 1950) · 2015Review
- The effect of the autoimmunity-associated gene, PTPN22, on a BXSB-derived model of lupus.Clinical immunology (Orlando, Fla.) · 2015Article
- Genetic Variations of PTPN2 and PTPN22: Role in the Pathogenesis of Type 1 Diabetes and Crohn's Disease.Frontiers in cellular and infection microbiology · 2015Review
- The tyrosine phosphatase PTPN22 discriminates weak self peptides from strong agonist TCR signals.Nature immunology · 2014Article
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
A C1858T (R620W) variation in the PTPN22 gene encoding the tyrosine phosphatase LYP is a major risk factor for human autoimmunity. LYP is a known negative regulator of signaling through the T cell receptor (TCR), and murine Ptpn22 plays a role in thymic selection. However, the mechanism of action of the R620W variant in autoimmunity remains unclear. One model holds that LYP-W620 is a gain-of-function phosphatase that causes alterations in thymic negative selection and/or thymic output of regulatory T cells (Treg) through inhibition of thymic TCR signaling. To test this model, we generated mice in which the human LYP-W620 variant or its phosphatase-inactive mutant are expressed in developing thymocytes under control of the proximal Lck promoter. We found that LYP-W620 expression results in diminished thymocyte TCR signaling, thus modeling a "gain-of-function" of LYP at the signaling level. However, LYP-W620 transgenic mice display no alterations of thymic negative selection and no anomalies in thymic output of CD4(+)Foxp3(+) Treg were detected in these mice. Lck promoter-directed expression of the human transgene also causes no alteration in thymic repertoire or increase in disease severity in a model of rheumatoid arthritis, which depends on skewed thymic selection of CD4(+) T cells. Our data suggest that a gain-of-function of LYP is unlikely to increase risk of autoimmunity through alterations of thymic selection and that LYP likely acts in the periphery perhaps selectively in regulatory T cells or in another cell type to increase risk of autoimmunity.
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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.