Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden.
Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden.
J Autoimmun. 2018 Jun;90:28-38. doi: 10.1016/j.jaut.2018.01.003. Epub 2018 Feb 3.
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.
蛋白酪氨酸磷酸酶非受体型 2（PTPN2）基因座中的非编码单核苷酸多态性与多种自身免疫性疾病有关，包括类风湿关节炎、1 型糖尿病和炎症性肠病。然而，这些 SNP 的功能后果还没有很好地描述。在此，我们在血细胞中表明，PTPN2 基因座中的 SNP 与 PTPN2 下游四个 CpG 位点的 DNA 甲基化水平以及这些 CpG 位点下游长非编码 RNA（lncRNA）LINC01882 的表达水平高度相关。我们观察到 LINC01882 主要在 T 细胞中表达，抗 CD3/CD28 激活幼稚 CD4 T 细胞下调 LINC01882 的表达。使用反义寡核苷酸和 RNA 干扰对 Jurkat T 细胞中的 LINC01882 敲低进行 RNA 测序分析，揭示了转录因子 ZEB1 和激酶 MAP2K4 的上调，两者都参与了 IL-2 的调节。总的来说，我们的数据表明 LINC01882 参与了 T 细胞的激活，并暗示这些非编码 SNP 在与 PTPN2 基因座相关的自身免疫中具有辅助作用。
