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Unraveling the functional implications of GWAS: how T cell protein tyrosine phosphatase drives autoimmune disease
Julie Zikherman, Arthur Weiss
Julie Zikherman, Arthur Weiss
Published November 14, 2011
Citation Information: J Clin Invest. 2011;121(12):4618-4621. https://doi.org/10.1172/JCI60001.
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Unraveling the functional implications of GWAS: how T cell protein tyrosine phosphatase drives autoimmune disease

Abstract

Genome-wide association studies (GWAS) have identified a large number of SNPs that are linked to human autoimmune diseases. However, the functional consequences of most of these genetic variations remain undefined. T cell protein tyrosine phosphatase (TCPTP, which is encoded by PTPN2) is a JAK/STAT and growth factor receptor phosphatase that has been linked to the pathogenesis of type 1 diabetes, rheumatoid arthritis, and Crohn’s disease by GWAS. In this issue of the JCI, Wiede and colleagues have generated a T cell–specific deletion of TCPTP and identified a novel role for this phosphatase as a negative regulator of TCR signaling. These data provide new insight as to how noncoding PTPN2 SNPs identified in GWAS could drive human autoimmune diseases.

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Julie Zikherman, Arthur Weiss

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Citations to this article (17)

Title and authors Publication Year
α-Methyl-Tryptophan Inhibits SLC6A14 Expression and Exhibits Immunomodulatory Effects in Crohn’s Disease
Su Y, Li J, Chen Y, Bao J, Lei Z, Ma M, Zhang W, Liu Q, Xu B, Hu T, Hu Y 		Journal of Inflammation Research 2025
Protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene polymorphisms (rs2542151, rs7234029) in Egyptian Behçet's disease patients: a preliminary report.
Attia DHS, Alkaffas M, Eissa M, Rashed L, Khattab RAM, Elzanaty R, Khattab RA, Samy LA 		Clinical rheumatology 2024
Inflammation versus regulation: how interferon-gamma contributes to type 1 diabetes pathogenesis
De George DJ, Ge T, Krishnamurthy B, Kay TW, Thomas HE 		Frontiers in Cell and Developmental Biology 2023
Common polymorphisms of protein tyrosine phosphate non-receptor type 2 gene are not associated with risk of Crohn’s disease in Indian
Chatterjee K, Dutta AK, Goel A, Aaron R, Balakrishnan V, Thomas A, John A, Jaleel R, David D, Kurien RT, Chowdhury S, Simon EG, Joseph A, Premkumar P, Pulimood AB 		World journal of gastrointestinal pathophysiology 2022
Modulation of PTPN2/22 Function by Spermidine in CRISPR-Cas9-Edited T-Cells Associated with Crohn’s Disease and Rheumatoid Arthritis
AM Shaw, A Qasem, SA Naser 		International journal of molecular sciences 2021
PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells
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Double-negative T cells remarkably promote neuroinflammation after ischemic stroke
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PTPN2 improved renal injury and fibrosis by suppressing STAT‐induced inflammation in early diabetic nephropathy
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An allelic variant in the intergenic region between ERAP1 and ERAP2 correlates with an inverse expression of the two genes
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RC Sharp, SA Beg, SA Naser 		World journal of gastroenterology : WJG 2018
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KD and, H El-Gabalawy 		Nature Reviews Rheumatology 2014
The tyrosine phosphatase PTPN22 discriminates weak self peptides from strong agonist TCR signals
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Network analysis identifies protein clusters of functional importance in juvenile idiopathic arthritis
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