T cells are influenced by a long non-coding RNA in the autoimmune associated PTPN2 locus
T cells are influenced by a long non-coding RNA in the autoimmune associated PTPN2 locus
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DOI：
10.1016/j.jaut.2018.01.003
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发表时间：
2018-06-01
影响因子：
12.8
通讯作者：
Padyukov, Leonid
中科院分区：
文献类型：
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作者：
Houtman, Miranda;Shchetynsky, Klementy;Padyukov, Leonid
蛋白酪氨酸磷酸酶非受体2型（PTPN 2）基因座中的非编码SNP与几种自身免疫性疾病有关，包括类风湿性关节炎、I型糖尿病和炎症性肠病。然而，这些SNPs的功能性后果的特点很差。在此，我们在血细胞中显示，PTPN 2基因座中的SNP与PTPN 2下游四个CpG位点处的DNA甲基化水平以及这些CpG位点下游的长非编码RNA（IncRNA）LINC 01882的表达水平高度相关。我们观察到LINC 01882主要在T细胞中表达，并且抗CD 3/CD 28激活的初始CD 4（+）T细胞下调LINC 01882的表达。使用反义寡核苷酸和RNA干扰的组合对Jurkat T细胞中LINC 01882敲低的RNA测序分析揭示了转录因子ZEB 1和激酶MAP 2K 4的上调，两者都参与IL-2调节。总的来说，我们的数据表明LINC 01882参与T细胞活化，并暗示这些非编码SNP在与PTPN 2基因座相关的自身免疫中的辅助作用。(C)2018作者爱思唯尔有限公司出版
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 (IncRNA) LINC01882 downstream of these CpG sites. We observed that LINC01882 is mainly expressed in T cells and that anti-CD3/CD28 activated naive CD4(+) T cells downregulate the expression of LINC01882. RNA sequencing analysis of LINC01882 knockdown in Jurkat T cells, using a combination of antisense oligo-nucleotides 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. (C) 2018 The Authors. Published by Elsevier Ltd.