ArticleThe Journal of clinical investigation2019
Reduced expression of phosphatase PTPN2 promotes pathogenic conversion of Tregs in autoimmunity.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Leveraging pleiotropy identifies common-variant associations with selective IgA deficiency.Clinical immunology (Orlando, Fla.) · 2024Pooled it
- Clonal sharing and plasticity of follicular CD4 + T cells across lymph nodes and tumors in non-small cell lung cancer.Nature communications · 2026Article
- Molecular Mechanisms and Targeted Therapies of PTPN2 in Metabolic Diseases: A Review.Biomolecules · 2026Review
- Loss of TET function in T regulatory cells yields ex-Treg cells biased toward T follicular helper cells, causing autoimmune diseases through autoantibody production.Frontiers in immunology · 2026Article
- TScience immunology · 2025Article
- Uncovering the individual immunotherapeutic roles of PTPN1 and PTPN2 in T cells during dual inhibition.iScience · 2025Article
- Loss of TET function in T regulatory cells yields ex-Treg cells biased toward T follicular helper cells, causing autoimmune diseases through autoantibody production.bioRxiv : the preprint server for biology · 2025Article
- Interaction between haploinsufficiency of PTPN2 and patient microbiome promotes autoimmune arthritis in mice.Journal of autoimmunity · 2025Article
- The TET-TDG axis in T cells and biological processes.International immunology · 2025Review
- Circulating exo-miRNA-27a-5p is a novel biomarker of the tofacitinib treatment response in rheumatoid arthritis.BMC rheumatology · 2025Article
- Osteoimmunology: Crosstalk Between T Cells and Osteoclasts in Osteoporosis.Clinical reviews in allergy & immunology · 2025Review
- Protein phosphatases in systemic autoimmunity.Immunometabolism (Cobham, Surrey) · 2025Review
- ABCD of IA: A multi-scale agent-based model of T cell activation in inflammatory arthritis.Biomaterials science · 2024Article
- PTPN2 Regulates Metabolic Flux to Affect β-Cell Susceptibility to Inflammatory Stress.Diabetes · 2024Article
- Article
- Immunotherapeutic implications of negative regulation by protein tyrosine phosphatases in T cells: the emerging cases of PTP1B and TCPTP.Frontiers in medicine · 2024Review
- Identification of human exTNature immunology · 2023Article
- Short-chain fatty acid-mediated epigenetic modulation of inflammatory T cells in vitro.Drug delivery and translational research · 2023Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
Corrections and comments
- Commented on byHow T2019
Authors and funding
23 authors at 7 institutions in 6 countries.
Funding
Abstract
Genetic variants at the PTPN2 locus, which encodes the tyrosine phosphatase PTPN2, cause reduced gene expression and are linked to rheumatoid arthritis (RA) and other autoimmune diseases. PTPN2 inhibits signaling through the T cell and cytokine receptors, and loss of PTPN2 promotes T cell expansion and CD4- and CD8-driven autoimmunity. However, it remains unknown whether loss of PTPN2 in FoxP3+ regulatory T cells (Tregs) plays a role in autoimmunity. Here we aimed to model human autoimmune-predisposing PTPN2 variants, the presence of which results in a partial loss of PTPN2 expression, in mouse models of RA. We identified that reduced expression of Ptpn2 enhanced the severity of autoimmune arthritis in the T cell-dependent SKG mouse model and demonstrated that this phenotype was mediated through a Treg-intrinsic mechanism. Mechanistically, we found that through dephosphorylation of STAT3, PTPN2 inhibits IL-6-driven pathogenic loss of FoxP3 after Tregs have acquired RORγt expression, at a stage when chromatin accessibility for STAT3-targeted IL-17-associated transcription factors is maximized. We conclude that PTPN2 promotes FoxP3 stability in mouse RORγt+ Tregs and that loss of function of PTPN2 in Tregs contributes to the association between PTPN2 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.