※ をクリックすると外部の論文のサイトが開きます。
論文
- タイトル
- タイトル（英）
- DNA methylation and multi-omics profiling of T cells uncovers chemotactic pathways and proliferation-linked hypomethylation in narcolepsy type 1.
- 参照URL
- https://researchmap.jp/narcolepsy/published_papers/52634243
- 著者
- 著者（英）
- Mihoko Shimada,Makoto Honda,Yoshiko Honda,Tohru Kodama,Yuki Hitomi,Katsushi Tokunaga,Taku Miyagawa
- 担当区分
- 概要
- 概要（英）
- Narcolepsy type 1 (NT1) is a chronic sleep disorder caused by a loss of orexin-producing cells in the brain and involves autoimmune mechanisms, including the presence of autoreactive T cells. In this study, we performed genome-wide DNA methylation analysis using both CD4+/CD8+ T cells from 42 NT1 patients and 42 controls across discovery and replication cohorts. To identify methylation changes more robustly associated with the disease, we prioritized differentially methylated regions (DMRs) over single-site differentially methylated positions (DMPs). Furthermore, to validate and interpret DMP-level associations, we integrated genome-wide genotype and gene expression data obtained from the same individuals. As a result, the DMR analysis identified 15 reproducible DMRs in CD4+ T cells and 5 in CD8+ T cells, with most DMRs shared between the two cell types. Shared DMRs included regions associated with CCL5 (p=2.1.E-02) and CCR4 (p=8.3.E-03). Integrative analysis with genotype and gene expression data also showed that the DMP related to S100A4, which promotes lymphocyte migration through CCR5 and CXCR3 receptors, was associated with the disease in CD4+ T cells. Pathway analysis of genes identified through both the DMR and integrative analyses indicated enrichment in cell chemotaxis-related pathways, suggesting that aberrant chemokine-mediated cell migration plays a central role in NT1 pathogenesis. Further, NT1-associated methylation changes were predominantly hypomethylation events, significantly enriched in non-promoter, non-CpG island regions (p=1.74E-102). We further observed that global hypomethylation levels were correlated with hypoSC, a mitotic index estimated from methylation data, highlighting increased T cell proliferation in NT1.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Sleep
- 巻
- 号
- 開始ページ
- 終了ページ
- 出版年月
- 2025年9月16日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1093/sleep/zsaf278
- 共同研究・競争的資金等の研究課題