Dysregulated long non-coding RNA in Sjögren's disease impacts both interferon and adaptive immune responses.
Dysregulated long non-coding RNA in Sjögren's disease impacts both interferon and adaptive immune responses.
复制标题
DOI：
10.1136/rmdopen-2022-002672
复制
发表时间：
2022-11
期刊：
影响因子：
6.2
通讯作者：
Lessard, Christopher J.
中科院分区：
文献类型：
--
作者：
Joachims, Michelle L.;Khatri, Bhuwan;Li, Chuang;Tessneer, Kandice L.;Ice, John A.;Stolarczyk, Anna M.;Means, Nicolas;Grundahl, Kiely M.;Glenn, Stuart B.;Kelly, Jennifer A.;Lewis, David M.;Radfar, Lida;Stone, Donald U.;Guthridge, Joel M.;James, Judith A.;Scofield, R. Hal;Wiley, Graham B.;Wren, Jonathan D.;Gaffney, Patrick M.;Montgomery, Courtney G.;Sivils, Kathy L.;Rasmussen, Astrid;Farris, A. Darise;Adrianto, Indra;Lessard, Christopher J.
干燥病 (SjD) 是一种自身免疫性疾病，其特征是外分泌腺炎症性破坏。具有 Ro/SSA 自身抗体 (SjDRo+) 的患者表现出更严重的疾病。长非编码 RNA (lncRNA) 是一类功能多样的非蛋白编码 RNA，其在自身免疫性疾病病理学中的作用尚未得到很好的表征。对SjD病例（n=23 Ro/SSA阴性（SjDRo−）；n=27 Ro/SSA阳性（SjDRo+）和健康对照（HC；n=27）进行全血RNA测序（RNA-seq）。差异表达（DE）转录本的生物信息学和通路分析（log2倍数变化≥2 或≤0.5；padj<0.05）用于预测lncRNA LINC01871 通过对 CRISPR 靶向 LINC01871 缺失 (LINC01871−/−) 的 HSB-2 细胞进行 RNA 测序分析和体外刺激分析，揭示了 SjD 病例中相对于 HC 的自身抗体特异性转录谱和 DE 转录物的不成比例下调。 RSAD2，在 SjDRo+ 中（r≥0.65 或≤−0.6）；在所有 SjD 病例中，四种反义 lncRNA 均表现出 IFN 调节的表达，LINC01871−/− 细胞的通路分析表明，LINC01871 在细胞毒性功能、分化和 IFNγ 诱导中发挥作用。 LINC01871 受钙调神经磷酸酶/NFAT 通路和原代人 T 细胞中的 T 细胞受体 (TCR) 信号传导调节，可被 IFNγ 诱导，并受钙调磷酸酶信号传导和 TCR 配体参与调节。改变的 LINC01871 表达可能会影响与 SjD 相关的失调的 T 细胞炎症通路。
Sjögren’s disease (SjD) is an autoimmune disease characterised by inflammatory destruction of exocrine glands. Patients with autoantibodies to Ro/SSA (SjDRo+) exhibit more severe disease. Long non-coding RNAs (lncRNAs) are a functionally diverse class of non-protein-coding RNAs whose role in autoimmune disease pathology has not been well characterised. Whole blood RNA-sequencing (RNA-seq) was performed on SjD cases (n=23 Ro/SSA negative (SjDRo−); n=27 Ro/SSA positive (SjDRo+) and healthy controls (HCs; n=27). Bioinformatics and pathway analyses of differentially expressed (DE) transcripts (log2 fold change ≥2 or ≤0.5; padj<0.05) were used to predict lncRNA function. LINC01871 was characterised by RNA-seq analyses of HSB-2 cells with CRISPR-targeted LINC01871 deletion (LINC01871−/−) and in vitro stimulation assays. Whole blood RNA-seq revealed autoantibody-specific transcription profiles and disproportionate downregulation of DE transcripts in SjD cases relative to HCs. Sixteen DE lncRNAs exhibited correlated expression with the interferon (IFN)-regulated gene, RSAD2, in SjDRo+ (r≥0.65 or ≤−0.6); four antisense lncRNAs exhibited IFN-regulated expression in immune cell lines. LINC01871 was upregulated in all SjD cases. RNA-seq and pathway analyses of LINC01871−/− cells implicated roles in cytotoxic function, differentiation and IFNγ induction. LINC01871 was induced by IFNγ in a myeloid cell line and regulated by calcineurin/NFAT pathway and T cell receptor (TCR) signalling in primary human T cells. LINC01871 influences expression of many immune cell genes and growth factors, is IFNγ inducible, and regulated by calcineurin signalling and TCR ligand engagement. Altered LINC01871 expression may influence the dysregulated T cell inflammatory pathways implicated in SjD.
登录
查看更多内容
影响因子：
64.5
作者：
Caielli S;Cardenas J;de Jesus AA;Baisch J;Walters L;Blanck JP;Balasubramanian P;Stagnar C;Ohouo M;Hong S;Nassi L;Stewart K;Fuller J;Gu J;Banchereau JF;Wright T;Goldbach-Mansky R;Pascual V
通讯作者：
Pascual V
影响因子：
--
作者：
He Y;Wang X
通讯作者：
Wang X
影响因子：
--
作者：
Greenwell-Wild, Teresa;Moutsopoulos, Niki M.;Gliozzi, Maria;Kapsogeorgou, Efstathia;Rangel, Zoila;Munson, Peter J.;Moutsopoulos, Haralampos M.;Wahl, Sharon M.
通讯作者：
Wahl, Sharon M.
影响因子：
5.7
作者：
Feng Y;Shen Y;Chen H;Wang X;Zhang R;Peng Y;Lei X;Liu T;Liu J;Gu L;Wang F;Yang Y;Bai J;Wang J;Zhao W;He A
通讯作者：
He A
影响因子：
5
作者：
Asatsuma, M;Ito, S;Igarashi, A
通讯作者：
Igarashi, A