系统性红斑狼疮和其他自身免疫性疾病中的表观遗传机制。
Epigenetic mechanisms in systemic lupus erythematosus and other autoimmune diseases.
机构信息
Department of Medicine, Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Trends Mol Med. 2011 Dec;17(12):714-24. doi: 10.1016/j.molmed.2011.07.005. Epub 2011 Aug 30.
Abstract
The pathogenic origin of autoimmune diseases can be traced to both genetic susceptibility and epigenetic modifications arising from exposure to the environment. Epigenetic modifications influence gene expression and alter cellular functions without modifying the genomic sequence. CpG-DNA methylation, histone tail modifications and microRNAs (miRNAs) are the main epigenetic mechanisms of gene regulation. Understanding the molecular mechanisms that are involved in the pathophysiology of autoimmune diseases is essential for the introduction of effective, target-directed and tolerated therapies. In this review, we summarize recent findings that signify the importance of epigenetic modifications in autoimmune disorders while focusing on systemic lupus erythematosus. We also discuss future directions in basic research, autoimmune diagnostics and applied therapy.
摘要
自身免疫性疾病的发病根源可追溯至遗传易感性和环境暴露引起的表观遗传修饰。表观遗传修饰影响基因表达并改变细胞功能，而不会改变基因组序列。CpG-DNA 甲基化、组蛋白尾部修饰和 microRNAs（miRNAs）是基因调控的主要表观遗传机制。了解参与自身免疫性疾病病理生理学的分子机制对于引入有效、靶向和耐受的治疗方法至关重要。在这篇综述中，我们总结了最近的发现，这些发现表明了表观遗传修饰在自身免疫性疾病中的重要性，重点是系统性红斑狼疮。我们还讨论了基础研究、自身免疫性诊断和应用治疗的未来方向。
相似文献
1
Epigenetic mechanisms in systemic lupus erythematosus and other autoimmune diseases.系统性红斑狼疮和其他自身免疫性疾病中的表观遗传机制。
Trends Mol Med. 2011 Dec;17(12):714-24. doi: 10.1016/j.molmed.2011.07.005. Epub 2011 Aug 30.
2
Epigenetics in lupus.狼疮中的表观遗传学。
Autoimmunity. 2014 Jun;47(4):213-4. doi: 10.3109/08916934.2014.915393.
3
The Role of Epigenetics in Autoimmune/Inflammatory Disease.表观遗传学在自身免疫/炎症性疾病中的作用。
Front Immunol. 2019 Jul 4;10:1525. doi: 10.3389/fimmu.2019.01525. eCollection 2019.
4
Effects of Major Epigenetic Factors on Systemic Lupus Erythematosus.主要表观遗传因素对系统性红斑狼疮的影响
Iran Biomed J. 2018 Sep;22(5):294-302. doi: 10.29252/ibj.22.5.294. Epub 2018 May 27.
5
MicroRNAs in lupus.狼疮中的微小RNA
Autoimmunity. 2014 Jun;47(4):272-85. doi: 10.3109/08916934.2014.915955.
6
Autoimmune disease in the epigenetic era: how has epigenetics changed our understanding of disease and how can we expect the field to evolve?表观遗传学时代的自身免疫性疾病：表观遗传学如何改变了我们对疾病的理解，以及我们能期待该领域如何发展？
Expert Rev Clin Immunol. 2015 Jan;11(1):45-58. doi: 10.1586/1744666X.2015.994507.
7
Epigenetic perspectives in systemic lupus erythematosus: pathogenesis, biomarkers, and therapeutic potentials.系统性红斑狼疮的表观遗传学观点：发病机制、生物标志物和治疗潜力。
Clin Rev Allergy Immunol. 2010 Aug;39(1):3-9. doi: 10.1007/s12016-009-8165-7.
8
Epigenetics changes associated to environmental triggers in autoimmunity.自身免疫中与环境触发因素相关的表观遗传学变化。
Autoimmunity. 2016;49(1):1-11. doi: 10.3109/08916934.2015.1086996. Epub 2015 Sep 15.
9
Epigenetic regulation of cytokine expression in systemic lupus erythematosus with special focus on T cells.系统性红斑狼疮中细胞因子表达的表观遗传调控，特别关注T细胞。
Autoimmunity. 2014 Jun;47(4):234-41. doi: 10.3109/08916934.2013.801462. Epub 2014 Apr 24.
10
Epigenetic histone code and autoimmunity.表观遗传组蛋白密码与自身免疫
Clin Rev Allergy Immunol. 2010 Aug;39(1):78-84. doi: 10.1007/s12016-009-8173-7.
引用本文的文献
1
Genome-Wide Impact of Folic Acid on DNA Methylation and Gene Expression in Lupus Adipocytes: An In Vitro Study on Obesity.叶酸对狼疮脂肪细胞DNA甲基化和基因表达的全基因组影响：一项关于肥胖的体外研究
Nutrients. 2025 Mar 20;17(6):1086. doi: 10.3390/nu17061086.
2
Alopecia Areata: Pathogenesis, Diagnosis, and Therapies.斑秃：发病机制、诊断与治疗
MedComm (2020). 2025 Apr 21;6(5):e70182. doi: 10.1002/mco2.70182. eCollection 2025 May.
3
Role of DNA Methylation in the Pathogenesis of Skin Disorders: Mechanisms, Inhibitors of Methylation-Related Enzyme, and Molecular Docking Studies.DNA甲基化在皮肤疾病发病机制中的作用：机制、甲基化相关酶抑制剂及分子对接研究
Biomed Res Int. 2025 Mar 27;2025:7002918. doi: 10.1155/bmri/7002918. eCollection 2025.
4
How (Ultra-)Rare Gene Variants Improve Our Understanding of More Common Autoimmune and Inflammatory Diseases.（超）罕见基因变异如何增进我们对更常见自身免疫性和炎症性疾病的理解。
ACR Open Rheumatol. 2025 Feb;7(2):e70003. doi: 10.1002/acr2.70003.
5
Protein phosphatases in systemic autoimmunity.系统性自身免疫中的蛋白磷酸酶。
Immunometabolism (Cobham). 2025 Feb 10;7(1):e00056. doi: 10.1097/IN9.0000000000000056. eCollection 2025 Jan.
6
Across ancestries, HLA-B∗08:01∼DRB1∗03:01 (DR3) and HLA-DQA∗01:02 (DR2) increase the risk to develop juvenile-onset systemic lupus erythematosus through low complement C4 levels.在不同血统中，HLA - B∗08:01∼DRB1∗03:01（DR3）和HLA - DQA∗01:02（DR2）通过低补体C4水平增加患青少年型系统性红斑狼疮的风险。
J Transl Autoimmun. 2025 Jan 7;10:100268. doi: 10.1016/j.jtauto.2025.100268. eCollection 2025 Jun.
7
Lupus Nephritis Biomarkers: A Critical Review.狼疮性肾炎生物标志物：批判性综述。
Int J Mol Sci. 2024 Jan 9;25(2):805. doi: 10.3390/ijms25020805.
8
Exploring the theranostic potentials of miRNA and epigenetic networks in autoimmune diseases: A comprehensive review.探讨 miRNA 和表观遗传网络在自身免疫性疾病中的治疗潜力：全面综述。
Immun Inflamm Dis. 2023 Dec;11(12):e1121. doi: 10.1002/iid3.1121.
9
Learning single-cell perturbation responses using neural optimal transport.利用神经最优传输学习单细胞扰动响应。
Nat Methods. 2023 Nov;20(11):1759-1768. doi: 10.1038/s41592-023-01969-x. Epub 2023 Sep 28.
10
The Epigenetic Contribution to the Pathogenesis of Psoriasis: Recent Advances.银屑病发病机制的表观遗传学贡献：最新进展。
Curr Med Chem. 2024;31(29):4621-4639. doi: 10.2174/0929867330666230503143824.
本文引用的文献
1
MicroRNA-126 regulates DNA methylation in CD4+ T cells and contributes to systemic lupus erythematosus by targeting DNA methyltransferase 1.微小RNA-126调节CD4+ T细胞中的DNA甲基化，并通过靶向DNA甲基转移酶1促进系统性红斑狼疮的发生。
Arthritis Rheum. 2011 May;63(5):1376-86. doi: 10.1002/art.30196.
2
HLA DRB1*1503 allelic haplotype predominance and associated immunodysregulation in systemic lupus erythematosus.HLA-DRB1*1503 等位基因单体型优势与系统性红斑狼疮的免疫失调相关。
Exp Mol Pathol. 2011 Oct;91(2):548-62. doi: 10.1016/j.yexmp.2011.03.006. Epub 2011 Apr 8.
3
Hypomethylation of LINE-1 but not Alu in lymphocyte subsets of systemic lupus erythematosus patients.系统性红斑狼疮患者淋巴细胞亚群中 LINE-1 的低甲基化，但 Alu 没有。
Clin Chim Acta. 2011 Jul 15;412(15-16):1457-61. doi: 10.1016/j.cca.2011.04.002. Epub 2011 Apr 7.
4
Epigenetics and autoimmunity, with special emphasis on methylation.表观遗传学与自身免疫，特别强调甲基化。
Keio J Med. 2011;60(1):10-6. doi: 10.2302/kjm.60.10.
5
Expression signature of microRNA-181-a reveals its crucial role in the pathogenesis of paediatric systemic lupus erythematosus.miR-181-a 的表达特征揭示了其在儿童系统性红斑狼疮发病机制中的关键作用。
Clin Exp Rheumatol. 2011 Mar-Apr;29(2):351-7. Epub 2011 Apr 19.
6
Promoter hypomethylation results in increased expression of protein phosphatase 2A in T cells from patients with systemic lupus erythematosus.启动子低甲基化导致系统性红斑狼疮患者 T 细胞中蛋白磷酸酶 2A 的表达增加。
J Immunol. 2011 Apr 1;186(7):4508-17. doi: 10.4049/jimmunol.1000340. Epub 2011 Feb 23.
7
MicroRNA expression profiles as biomarkers of minor salivary gland inflammation and dysfunction in Sjögren's syndrome.微小RNA表达谱作为干燥综合征中小唾液腺炎症和功能障碍的生物标志物
Arthritis Rheum. 2011 Feb;63(2):535-44. doi: 10.1002/art.30131.
8
Altered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation.微小RNA-203在类风湿性关节炎滑膜成纤维细胞中的表达变化及其在成纤维细胞活化中的作用
Arthritis Rheum. 2011 Feb;63(2):373-81. doi: 10.1002/art.30115.
9
The epigenetics of autoimmunity.自身免疫的表观遗传学。
Cell Mol Immunol. 2011 May;8(3):226-36. doi: 10.1038/cmi.2010.78. Epub 2011 Jan 31.
10
Epigenetics in lupus.狼疮的表观遗传学。
Ann N Y Acad Sci. 2011 Jan;1217:154-65. doi: 10.1111/j.1749-6632.2010.05831.x. Epub 2011 Jan 11.
Zotero 插件