Unraveling the functional implications of GWAS: How T cell protein tyrosine phosphatase drives autoimmune disease

Division of Rheumatology, Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, UCSF, San Francisco, California, USA.
The Journal of clinical investigation (Impact Factor: 13.22). 11/2011; 121(12):4618-21. DOI: 10.1172/JCI60001
Source: PubMed


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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Available from: Arthur Weiss, Jun 30, 2014
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    • "PTPN2 encodes for the ubiquitously expressed T cell protein tyrosine phosphatase (TCPTP), a JAK/STAT and growth factor receptor phosphatase that has been linked with the pathogenesis of type 1 diabetes mellitus, rheumatoid arthritis and Crohn’s disease by GWAS findings of non-coding SNP associations. Mouse and human studies have shown that reduced expression of TCPTP may drive autoimmune pathologies by enhancing signalling downstream of the T cell receptor (TCR), cytokines, or growth factors to produce a pro-inflammatory cytokine milieu [65]. "
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