ArticleGenes and immunity2011
An autoimmune-associated variant in PTPN2 reveals an impairment of IL-2R signaling in CD4(+) T cells.
Article in Genes and immunity, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
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Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- Regulation of TCR signalling by tyrosine phosphatases: from immune homeostasis to autoimmunity.Immunology · 2012Pooled it
- Type 1 diabetes-associated IL2RA variation lowers IL-2 signaling and contributes to diminished CD4+CD25+ regulatory T cell function.Journal of immunology (Baltimore, Md. : 1950) · 2012Trial
- 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
- Uncovering the individual immunotherapeutic roles of PTPN1 and PTPN2 in T cells during dual inhibition.iScience · 2025Article
- Interaction between haploinsufficiency of PTPN2 and patient microbiome promotes autoimmune arthritis in mice.Journal of autoimmunity · 2025Article
- Data-driven projections of candidate enhancer-activating SNPs in immune regulation.BMC genomics · 2025Article
- Protein phosphatases in systemic autoimmunity.Immunometabolism (Cobham, Surrey) · 2025Review
- Impact of genotyping (Frontiers in endocrinology · 2025Article
- Regulatory T cell dysfunction and immunotherapeutic breakthroughs in type 1 diabetes.Frontiers in endocrinology · 2025Review
- Protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene polymorphisms (rs2542151, rs7234029) in Egyptian Behçet's disease patients: a preliminary report.Clinical rheumatology · 2024Article
- Monocyte-macrophages modulate intestinal homeostasis in inflammatory bowel disease.Biomarker research · 2024Review
- ABCD of IA: A multi-scale agent-based model of T cell activation in inflammatory arthritis.Biomaterials science · 2024Article
- Tipping the balance in autoimmunity: are regulatory t cells the cause, the cure, or both?Molecular and cellular pediatrics · 2024Review
- PTPN2 Regulates Metabolic Flux to Affect β-Cell Susceptibility to Inflammatory Stress.Diabetes · 2024Article
- Immunotherapeutic implications of negative regulation by protein tyrosine phosphatases in T cells: the emerging cases of PTP1B and TCPTP.Frontiers in medicine · 2024Review
- Insulin-like Growth Factor-1 Synergizes with IL-2 to Induce Homeostatic Proliferation of Regulatory T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- A small molecule inhibitor of PTP1B and PTPN2 enhances T cell anti-tumor immunity.Nature communications · 2023Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
The IL-2/IL-2R signaling pathway has an important role in autoimmunity. Several genes identified in genome-wide association (GWA) studies encode proteins in the IL-2/IL-2R signaling cascade that are associated with autoimmune diseases. One of these, PTPN2, encodes a protein tyrosine phosphatase that is highly expressed in T cells and regulates cytokine signaling. An intronic risk allele in PTPN2, rs1893217(C), correlated with decreased IL-2R signaling in CD4(+) T cells as measured by phosphorylation of STAT5 (phosphorylated STAT5 (pSTAT5)). We modeled an additive single nucleotide polymorphism (SNP) genotype, in which each copy of the risk allele conferred a decrease in IL-2R signaling (P=4.4 × 10(-8)). Decreased pSTAT5 impacted IL-2Rβ chain signaling resulting in reduced FOXP3 expression in activated cells. This phenotype was not due to overt differences in expression of the IL-2R, molecules in the IL-2R signaling cascade or defects in STAT5. However, the rs1893217(C) risk variant did correlate with decreased PTPN2 expression in CD4(+)CD45RO T cells (P=0.0002). Thus, the PTPN2rs1893217(C) risk allele associated with reduced pSTAT5 in response to IL-2 and reduced PTPN2 expression. Together, these data suggest that decreased expression of PTPN2 may indirectly modulate IL-2 responsiveness. These findings, identified through genotype/phenotype relationships, may lead to identification of novel mechanisms underlying dysregulation of cytokine signaling in 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.