T cells are influenced by a long non-coding RNA in the autoimmune associated PTPN2 locus

Publication date: Available online 3 February 2018
Source:Journal of Autoimmunity
Author(s): Miranda Houtman, Klementy Shchetynsky, Karine Chemin, Aase Haj Hensvold, Daniel Ramsköld, Karolina Tandre, Maija-Leena Eloranta, Lars Rönnblom, Steffen Uebe, Anca Irinel Catrina, Vivianne Malmström, Leonid Padyukov
Non-coding SNPs in the protein tyrosine phosphatase non-receptor type 2 (PTPN2) locus have been linked with several autoimmune diseases, including rheumatoid arthritis, type I diabetes, and inflammatory bowel disease. However, the functional consequences of these SNPs are poorly characterized. Herein, we show in blood cells that SNPs in the PTPN2 locus are highly correlated with DNA methylation levels at four CpG sites downstream of PTPN2 and expression levels of the long non-coding RNA (lncRNA) LINC01882 downstream of these CpG sites. We observed that LINC01882 is mainly expressed in T cells and that anti-CD3/CD28 activated naïve CD4⁺ T cells downregulate the expression of LINC01882. RNA sequencing analysis of LINC01882 knockdown in Jurkat T cells, using a combination of antisense oligonucleotides and RNA interference, revealed the upregulation of the transcription factor ZEB1 and kinase MAP2K4, both involved in IL-2 regulation. Overall, our data suggests the involvement of LINC01882 in T cell activation and hints towards an auxiliary role of these non-coding SNPs in autoimmunity associated with the PTPN2 locus.



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