title: 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.
authors.affiliation: Division of Rheumatology, Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, UCSF, San Francisco, California, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Zikherman
authors.forename: Arthur
authors.initials: A
authors.lastname: Weiss
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology*; D007108:Immune Tolerance / Q000276:immunology*; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000201:enzymology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; C516653:Ptpn2 protein, mouse
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