T细胞DNA低甲基化在SLE的研究进展

系统性红斑狼疮是一种自身免疫性疾病，越来越多的研究认为DNA甲基化异常在其发病中起重要作用。为此，总结了系统性红斑狼疮的甲基化特征、T细胞发生DNA低甲基化的机制、DNA低甲基化引起SLE的相关基因变化、基因活性的变化引发系统性红斑狼疮的主要途径，其中重点综述了淋巴细胞功能相关抗原1、穿孔素、CD70分子过度表达而引发系统性红斑狼疮的3种途径的新进展。     

T细胞DNA低甲基化在系统性红斑狼疮发病中的作用

当各种原因使患者出现Ｔ细胞ＤＮＡ低甲基化时，可能导致白细胞功能相关抗原－１，白介素－６，Ｈａ－ｒａｓ等因子的过度表达，从而激活Ｔ细胞使之成为自身反应性细胞。通过这种自身反应性细胞与Ｂ细胞的相互作用，引起多克隆Ｂ细胞的活化，最终病理性自身抗体的产生及系统性红斑狼疮的发生。     

T细胞DNA低甲基化在SLE的研究进展

系统性红斑狼疮是一种自身免疫性疾病,越来越多的研究认为DNA甲基化异常在其发病中起重要作用。为此,总结了系统性红斑狼疮的甲基化特征、T细胞发生DNA低甲基化的机制、DNA低甲基化引起SLE的相关基因变化、基因活性的变化引发系统性红斑狼疮的主要途径,其中重点综述了淋巴细胞功能相关抗原1、穿孔素、CD70分子过度表达而引发系统性红斑狼疮的3种途径的新进展。     

T细胞DNA低甲基化在系统性红斑狼疮发病中的作用

当各种原因使患者出现T细胞DNA低甲基化时 ,可能导致白细胞功能相关抗原 1、白介素 6、Ha ras等因子的过度表达 ,从而激活T细胞使之成为自身反应性细胞。通过这种自身反应性细胞与B细胞的相互作用 ,引起多克隆B细胞的活化 ,最终导致病理性自身抗体的产生及系统性红斑狼疮的发生。     

组织常驻记忆T细胞在皮肤病的研究进展

组织常驻记忆T细胞（tissue-resident memory T cells, TRM）是最近发现的记忆T淋巴细胞亚群。这类细胞不参与血液循环,当病原体被消除后仍长期存在于组织中,在病原再次侵入时即刻发挥保护作用。但是,TRM异常激活可能参与了自身免疫和炎症性疾病的发病机制。近年来,这类细胞在银屑病、白癜风、黑素瘤、变应性接触性皮炎等皮肤病中均被描述过。该文就TRM在皮肤病中的研究进展做一综述。     

DNA甲基化与皮肤肿瘤的研究进展

DNA甲基化是表观遗传学的重要内容之一,该DNA修饰方式在不改变基因序列的前提下实现对基因表达的调控.多项研究证实,DNA甲基化异常与黑素瘤、皮肤基底细胞癌、皮肤鳞状细胞癌、皮肤T细胞淋巴瘤的发生密切相关,而DNA甲基化检测技术为检测DNA甲基化提供技术平台.通过甲基化检测技术分析基因异常甲基化已成为当前皮肤肿瘤早期诊断、治疗、预后评估等的方向.     

长链非编码RNA在T细胞相关性皮肤病中的作用

长链非编码RNA(lncRNA)是长度＞200个核苷酸且不能编码蛋白的RNA.研究发现lncRNA可以调节T细胞的增殖、分化、凋亡等过程.T细胞在某些皮肤疾病的发病机制中具有重要作用,良性疾病如银屑病、特应性皮炎、白癜风和扁平苔藓,恶性疾病如蕈样肉芽肿、Sézary综合征和间变性大细胞淋巴瘤.本文就lncRNA在T细胞...     

恶性黑素瘤DNA甲基化的研究进展

恶性黑素瘤是一种皮肤起源的恶性肿瘤,其发生率和致死率在世界范围逐年上升.表观遗传学是一种涉及基因功能但不涉及DNA序列改变的遗传机制,DNA甲基化是其中最重要的机制之一,其作为连接表型与基因型重要纽带,是恶性黑素瘤发生发展中具有特异性和标志性的遗传学事件.通过逆转这些异常的甲基化状态实现更有针对性的治疗是新的研究方向.     

调节T细胞及其在皮肤病中的作用

调节T细胞是一类具有免疫抑制作用的细胞群，通过细胞接触抑制或抑制性细胞因子主动抑制自身免疫性T细胞。对于维持机体免疫自稳、预防自身免疫病具有极其重要的作用。最近研究表明，调节T细胞与银屑病、系统性红斑狼疮等自身免疫性皮肤病和皮肤肿瘤的发病存在相关性．综述了调节T细胞在这些皮肤病的发病机制中的作用。     

羟氯喹逆转紫外线诱导的SLE患者CD4+T细胞DNA低甲基化的研究

目的 探讨羟氯喹对紫外线诱导的SLE患者CD4+ T细胞基因组DNA低甲基化的作用。方法 选择SLE患者组30例,正常人对照组10例。 磁珠分选SLE患者组和正常人对照组外周血CD4+ T细胞,311 nm窄谱UVB照射,加入羟氯喹共培养,检测各组间基因组DNA甲基化表达水平。结果 SLE患者组CD4+ T细胞DNA甲基化水平（3.922 ± 2.215）%低于正常人对照组［（10.210 ± 5.573）%,t = 3.450,P = 0.026］;SLE活动组患者CD4+ T细胞经45 mJ/cm2和100 mJ/cm2 UVB照射后DNA甲基化水平为（1.784 ± 1.033）%和（1.932 ± 1.844）%,均显著低于活动期患者未照射组［（3.922 ± 2.215）%,t = 3.000、4.118,P值均 < 0.05］。经100 mJ/cm2 UVB照射后,活动期患者DNA甲基化水平（1.932 ± 1.844）%显著低于稳定期患者照射组 ［（7.235 ± 3.846）%,t = 2.648,P < 0.05］和正常人对照组［（5.472 ± 5.573）%,t = 3.000,P < 0.05］。SLE活动组T细胞经45和100 mJ/cm2 UVB照射后,加用羟氯喹结果DNA甲基化水平为（4.698 ± 1.948）%和（8.698 ± 3.151）%,均比照射未加羟氯喹组显著升高（t = 4.827、3.184,P值均 < 0.05）;经45 mJ/cm2 UVB照射前后均加羟氯喹组DNA甲基化水平（5.404 ± 2.308）%比照射未加羟氯喹组（1.784 ± 1.033）%显著升高,t = 4.827,P < 0.01。结论 羟氯喹可以逆转紫外线诱导的SLE患者CD4+ T细胞DNA低甲基化,羟氯喹对活动期SLE患者更为明显。     

Reduction in DNA methyltransferases and alteration of DNA methylation pattern associate with mouse skin ageing

Understanding molecular mechanisms of skin ageing is critical for developing effective anti‐ageing strategies. Recently, it has been suggested that epigenetics maybe be involved in tissue ageing and age‐related diseases; however, the evidence regarding skin ageing has been very limited. We ran a pilot study in mouse skin to test whether DNA methyltransferases (Dnmts), DNA demethylases such as ten‐eleven translocation enzymes (Tets) and DNA methylation of gene promoters change with age by quantitative RT‐PCR and methylated DNA immunoprecipitation (MeDIP)‐chip. We discovered that the expression of Dnmt3a, Dnmt3b and Tet2 declines significantly with skin ageing. The genome‐wide DNA methylation analysis indicates that both hypermethylation and hypomethylation in promoters of genes are taken place. Functional category of those genes suggests that inhibition of cell proliferation and activation of immune response are important adaptations likely induced by skin ageing. These findings shed new light on epigenetic regulation of skin ageing.     

炎症性皮肤病的DNA异常甲基化

DNA甲基化是一种重要的不改变DNA序列,但可影响基因表达水平并遗传的表观遗传学事件.随着DNA甲基化检测方法的日趋完善,有越来越多的研究表明,DNA异常甲基化与炎症性皮肤病相关.有研究证实或提示,DNA异常甲基化可能与多种炎症性皮肤疾病的发病机制密切相关,如银屑病、系统性红斑狼疮、特应性皮炎、系统性硬皮病,其他尚包括雄激素性脱发、慢性湿疹和天疱疮等,但研究并不能清楚地解释异常的甲基化模式如何在疾病中发挥具体的生物学作用.随着研究的深入,可对相关疾病的研究提供新的思路.     

Immunoregulation of skin sensitization and regulatory T cells

It is well established that, in common with other adaptive immune responses, the acquisition of skin sensitization is carefully orchestrated and finely controlled. This is achieved in a number of ways. However, in recent years, there has been an increasing interest in the roles that regulatory T cells (Tregs) play in allergic contact dermatitis. Here, we review briefly the phenotype and function of Tregs, and consider how they may impact on various aspects of skin sensitization, including: inter-individual differences in susceptibility; variations in the potency of chemical allergens; and the prevention of excessive, and potentially damaging, levels of sensitization.     

DNA甲基化与银屑病相关基因的研究进展

DNA甲基化作为重要的表观遗传学现象之一,对基因的表达、细胞分化与增殖等发挥重要的调控功能.银屑病是一种由多基因多因素共同作用的具有遗传背景的复杂疾病,其组织病理特征为表皮过度增殖等表现.近年来关于DNA甲基化与银屑病相关基因p14、p16、p21、HLA-C、SHP-1基因的研究成为热点.概述DNA甲基化机制及主要的甲基化检测方法,并阐述银屑病相关基因的甲基化的研究现状.     

黑素瘤与DNA甲基化研究进展

黑素瘤作为一种侵袭性强的皮肤恶性肿瘤,在发病率和死亡率方面都在上升,目前仍缺乏较为有效的治疗手段.近年来,随着人们对黑素瘤认识的逐渐深入,黑素瘤的表观遗传学修饰特别是在DNA甲基化方面的研究也受到广泛关注.DNA甲基化在肿瘤细胞中的改变相对较常见,包括黑素瘤细胞.因此,DNA甲基化相关基因可以作为黑素瘤早期筛查、诊断、预后、治疗分期以及治疗后监测的生物标记.     

Abnormal DNA methylation in T cells from patients with subacute cutaneous lupus erythematosus

Background Impaired methylation of T‐cell DNA is thought to contribute to the development of systemic lupus erythematosus. However, it is unknown whether T‐cell hypomethylation is a factor in other, less severe, forms of lupus erythematosus such as subacute cutaneous lupus erythematosus (SCLE). Objectives To investigate global DNA methylation and the expression of genes that regulate methylation in T cells of patients with SCLE. Methods We quantified global methylcytosine levels in CD4+ and CD8+ T cells from 12 patients with SCLE and nine healthy controls. mRNA levels of DNA methyltransferases (DNMTs), methylated CpG binding proteins (MBDs) and CD11a were measured by real‐time quantitative polymerase chain reaction. Results CD4+ T‐cell DNA from patients with SCLE was hypomethylated relative to controls (P = 0·002). DNMT1 and DNMT3a mRNA levels were significantly lower in CD4+ T cells from SCLE patients than in controls (P = 0·027 and P = 0·004, respectively). Relative to controls, MBD1, MBD3 and MBD4 mRNA levels were significantly higher in SCLE CD4+ cells (P < 0·001, P < 0·001 and P = 0·001, respectively), whereas MECP2 and MBD4 mRNA expression were significantly increased in SCLE CD8+ T cells (P = 0·001 and P = 0·001, respectively). DNMT1 expression positively correlated with CD4+ T‐cell DNA methylation within our SCLE patient cohort (r = 0·590, P = 0·044). CD11a mRNA expression was significantly increased in SCLE CD4+ T cells relative to controls (P = 0·044) and negatively correlated with DNA methylation (r = ?0·669, P = 0·049). Conclusions These data suggest that aberrant regulation of DNA methylation in CD4+ T cells is associated with the development of SCLE.     

Mechanisms in allergic skin disorders

Background Allergic skin disorders are initiated and maintained through the action and interaction between resident tissue cells, infiltrating leucocytes and mediators. Review The major cellular components of the skin immune system are keratinocytes, dendritic cells such as epidermal Langerhans cells (LCs) and dermal dendritic cells, mast cells and fibroblasts. Following an allergenic stimulus, inflammatory and immunocompetent cells accumulate in the epidermis and dermis, giving rise to specific clinical and histological manifestations. Leucocytes which accumulate in the inflammatory focus attract more leucocytes and stimulate the resident cell population. Primary mediators, released by resident cells upon stimulation, play a vital role in initiating and controlling inflammation. The mediators induce vascular endothelial cells to express adhesion molecules, which mediate migration of leucocytes into the dermis, where chemotactic factors attract them to the inflammatory focus. Activation of trapped T-lymphocytes by antigen-presenting cells (APCs) is followed by the release of inflammatory cytokines. Allergic contact dermatitis (ACD) depends on the activation of specifically sensitised T-cells, and epidermal LCs are the primary APCs. Most contact allergens are small, chemically reactive moleculed and CD4⁺ Th1 type T-cells are the target cells. Atopic dermatitis is a chronic eczematous condition, involving antibody IgE, LCs and dermal dendritic cells as the APCs, with Th2 T-lymphocytes as the target cells. Urticaria comprises a heterogeneous group of conditions, characterised by a wheal and flare reaction. Mast cells are the principal source of mediators involved and histamine is the most important of these.