An autoimmune-associated variant in PTPN2 reveals an impairment of IL-2R signaling in CD4(+) T cells.

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

SUBMITTER: Long SA 

PROVIDER: S-EPMC3058680 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature