T细胞DNA甲基化在部分皮肤病中的研究进展
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摘要
DNA甲基化是一种常见的表观遗传学修饰途径,与多种皮肤病的发病机制密切相关。T细胞包括CD8~+T细胞、CD4~+T细胞等。T细胞参与多种皮肤病如银屑病、系统性红斑狼疮(systemic lupus erythematosus,SLE)、系统性硬皮病(systemic scleroderma,SS)、原发性干燥综合征(primary Sjogren’s syndrome,pSS)等疾病的免疫应答过程,是参与疾病发生发展的重要调节性细胞。本文主要是从T细胞DNA甲基化的角度出发,对疾病的发病机制及研究进展进行综述。
DNA methylation is a common modification pathway in epigenetics, which is closely related to the pathogenesis of various skin disorders. T cells include CD8~+ T cells, CD4~+ T cells and so on, which involve in immune responses and work as important regulatory cells in the development of skin diseases such as psoriasis, systemic lupus erythematosus, systemic scleroderma, and primary Sjogren's syndrome. The update on the pathogenesis and research progress of these diseases, particularely from the point view of DNA methylation in T cells, is made.
DNA methylation is a common modification pathway in epigenetics, which is closely related to the pathogenesis of various skin disorders. T cells include CD8~+ T cells, CD4~+ T cells and so on, which involve in immune responses and work as important regulatory cells in the development of skin diseases such as psoriasis, systemic lupus erythematosus, systemic scleroderma, and primary Sjogren's syndrome. The update on the pathogenesis and research progress of these diseases, particularely from the point view of DNA methylation in T cells, is made.
引文
[1] Deng Y, Chang C, Lu Q. The Inflammatory Response in Psoriasis: a Comprehensive Review[J]. Clin Rev Allergy Immunol,2016,50(3):377-389.
[2] Pollock RA, Abji F, Gladman DD. Epigenetics of psoriatic disease: A systematic review and critical appraisal[J]. J Autoimmun,2017,78:29-38.
[3] Long HK, King HW, Patient RK, et al. Protection of CpG islands from DNA methylation is DNA-encoded and evolutionarily conserved[J]. Nucleic Acids Res,2016,44(14):6693-6706.
[4] Portela A, Esteller M. Epigenetic modifications and human disease[J]. Nat Biotechnol,2010,28(10):1057-1068.
[5] Bird AP. DNA methylation and the frequency of CpG in animal DNA[J]. Nucleic Acids Res,1980,8(7):1499-1504.
[6] Davegardh C, Garcia-Calzon S, Bacos K, et al. DNA methylation in the pathogenesis of type 2 diabetes in humans[J]. Mol Metab,2018,14:12-25.
[7] Fece de la Cruz F, Corcoran RB. Methylation in cell-free DNA for early cancer detection[J]. Ann Oncol,2018,29(6):1351-1353.
[8] Fransquet PD, Lacaze P, Saffery R, et al. Blood DNA methylation as a potential biomarker of dementia: A systematic review[J]. Alzheimers Dement,2018,14(1):81-103.
[9] Robertson KD. DNA methylation and human disease[J]. Nat Rev Genet,2005,6(8):597-610.
[10] Hodges E, Smith AD, Kendall J, et al. High definition profiling of mammalian DNA methylation by array capture and single molecule bisulfite sequencing[J]. Genome Res,2009,19(9):1593-1605.
[11] Edwards JR, Yarychkivska O, Boulard M, et al. DNA methylation and DNA methyltransferases[J]. Epigenetics Chromatin,2017,10:23.
[12] Chodavarapu RK, Feng S, Bernatavichute YV, et al. Relationship between nucleosome positioning and DNA methylation[J]. Nature,2010,466(7304):388-392.
[13] Hirahara K, Nakayama T. CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm[J]. Int Immunol,2016,28(4):163-171.
[14] Buckner JH. Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases[J]. Nat Rev Immunol,2010,10(12):849-859.
[15] Wang Z, Chang C, Lu Q. Epigenetics of CD4+ T cells in autoimmune diseases[J]. Curr Opin Rheumatol,2017,29(4):361-368.
[16] Ouyang H, Shi YB, Su N, et al. Abnormality and significance of interleukin-9 and CD4(+)interleukin-9(+) T-cells in peripheral blood of patients with systemic lupus erythematosus[J]. Zhonghua Yi Xue Za Zhi,2013,93(2):99-103.
[17] Singh TP, Schon MP, Wallbrecht K, et al. Involvement of IL-9 in Th17-associated inflammation and angiogenesis of psoriasis[J]. PLoS One,2013,8(1):e51752.
[18] Albanesi C. Keratinocytes in allergic skin diseases[J]. Curr Opin Allergy Clin Immunol,2010,10(5):452-456.
[19] Tokura Y. Th17 cells and skin diseases[J]. Nihon Rinsho Meneki Gakkai Kaishi,2012,35(5):388-392.
[20] Fujita H. The role of IL-22 and Th22 cells in human skin diseases[J]. J Dermatol Sci,2013,72(1):3-8.
[21] 秦思, 温炬, 郑荣昌,等.T细胞在银屑病与特应性皮炎发病机制中的研究进展[J].广东医学,2013,(7):1126-1129.
[22] Perera GK, Di Meglio P, Nestle FO. Psoriasis[J]. Annu Rev Pathol,2012,7:385-422.
[23] Lowes MA, Suarez-Farinas M, Krueger JG. Immunology of psoriasis[J]. Annu Rev Immunol,2014,32:227-255.
[24] Schakel K, Schon MP, Ghoreschi K. Pathogenesis of psoriasis[J]. Hautarzt,2016,67(6):422-431.
[25] Grayson M. Psoriasis[J]. Nature,2012,492(7429):S49.
[26] Zhang P, Zhao M, Liang G, et al. Whole-genome DNA methylation in skin lesions from patients with psoriasis vulgaris[J]. J Autoimmun,2013,41:17-24.
[27] Zhou F, Shen C, Xu J, et al. Epigenome-wide association data implicates DNA methylation-mediated genetic risk in psoriasis[J]. Clin Epigenetics,2016,8:131.
[28] Zhou F, Wang W, Shen C, et al. Epigenome-wide association analysis identified nine skin DNA methylation loci for psoriasis[J]. J Invest Dermatol,2016,136(4):779-787.
[29] Dozmorov MG, Coit P, Maksimowicz-McKinnon K, et al. Age-associated DNA methylation changes in naive CD4+ T cells suggest an evolving autoimmune epigenotype in aging T cells[J]. Epigenomics,2017,9(4):429-445.
[30] Zhao M, Qin J, Yin H, et al. Distinct epigenomes in CD4+ T cells of newborns, middle-ages and centenarians[J]. Sci Rep,2016,6:38411.
[31] Han J, Park SG, Bae JB, et al. The characteristics of genome-wide DNA methylation in naive CD4+ T cells of patients with psoriasis or atopic dermatitis[J]. Biochem Biophys Res Commun,2012,422(1):157-163.
[32] Park GT, Han J, Park SG, et al. DNA methylation analysis of CD4+ T cells in patients with psoriasis[J]. Arch Dermatol Res,2014,306(3):259-268.
[33] Gervin K, Vigeland MD, Mattingsdal M, et al. DNA methylation and gene expression changes in monozygotic twins discordant for psoriasis: identification of epigenetically dysregulated genes[J]. PLoS Genet,2012,8(1):e1002454.
[34] Ngalamika O, Liang G, Zhao M, et al. Peripheral whole blood FOXP3 TSDR methylation: a potential marker in severity assessment of autoimmune diseases and chronic infections[J]. Immunol Invest,2015,44(2):126-136.
[35] Huang L, Yang Y, Kuang Y, et al. The Impact of T cell vaccination in alleviating and regulating systemic lupus erythematosus manifestation[J]. J Immunol Res,2016,2016:5183686.
[36] Coit P, Jeffries M, Altorok N, et al. Genome-wide DNA methylation study suggests epigenetic accessibility and transcriptional poising of interferon-regulated genes in naive CD4+ T cells from lupus patients[J]. J Autoimmun,2013,43:78-84.
[37] Absher DM, Li X, Waite LL, et al. Genome-wide DNA methylation analysis of systemic lupus erythematosus reveals persistent hypomethylation of interferon genes and compositional changes to CD4+ T-cell populations[J]. PLoS Genet,2013,9(8):e1003678.
[38] Coit P, Dozmorov MG, Merrill JT, et al. Epigenetic reprogramming in naive CD4+ T cells favoring T cell activation and Non-Th1 effector T cell immune response as an early event in lupus flares[J]. Arthritis Rheumatol,2016,68(9):2200-2209.
[39] Coit P, Renauer P, Jeffries MA, et al. Renal involvement in lupus is characterized by unique DNA methylation changes in naive CD4+ T cells[J]. J Autoimmun,2015,61:29-35.
[40] Zhao M, Wang J, Liao W, et al. Increased 5-hydroxymethylcytosine in CD4(+) T cells in systemic lupus erythematosus[J]. J Autoimmun,2016,69:64-73.
[41] Zhao M, Liu S, Luo S, et al. DNA methylation and mRNA and microRNA expression of SLE CD4+ T cells correlate with disease phenotype[J]. J Autoimmun,2014,54:127-136.
[42] Alexander T, Sattler A, Templin L, et al. Foxp3+ Helios+ regulatory T cells are expanded in active systemic lupus erythematosus[J]. Ann Rheum Dis,2013,72(9):1549-1558.
[43] Konya C, Paz Z, Tsokos GC. The role of T cells in systemic lupus erythematosus: an update[J]. Curr Opin Rheumatol,2014,26(5):493-501.
[44] Lei W, Luo Y, Yan K, et al. Abnormal DNA methylation in CD4+ T cells from patients with systemic lupus erythematosus, systemic sclerosis, and dermatomyositis[J]. Scand J Rheumatol,2009,38(5):369-374.
[45] Jiang H, Xiao R, Lian X, et al. Demethylation of TNFSF7 contributes to CD70 overexpression in CD4+ T cells from patients with systemic sclerosis[J]. Clinical Immunol,2012,143(1):39-44.
[46] Wang YY, Wang Q, Sun XH, et al. DNA hypermethylation of the forkhead box protein 3 (FOXP3) promoter in CD4+ T cells of patients with systemic sclerosis[J]. Br J Dermatol,2014,171(1):39-47.
[47] Lian X, Xiao R, Hu X, et al. DNA demethylation of CD40l in CD4+ T cells from women with systemic sclerosis: a possible explanation for female susceptibility[J]. Arthritis Rheum,2012,64(7):2338-2345.
[48] Yin H, Zhao M, Wu X, et al. Hypomethylation and overexpression of CD70 (TNFSF7) in CD4+ T cells of patients with primary Sj?gren’s syndrome[J]. J Dermatol Science,2010,59(3):198-203.
[2] Pollock RA, Abji F, Gladman DD. Epigenetics of psoriatic disease: A systematic review and critical appraisal[J]. J Autoimmun,2017,78:29-38.
[3] Long HK, King HW, Patient RK, et al. Protection of CpG islands from DNA methylation is DNA-encoded and evolutionarily conserved[J]. Nucleic Acids Res,2016,44(14):6693-6706.
[4] Portela A, Esteller M. Epigenetic modifications and human disease[J]. Nat Biotechnol,2010,28(10):1057-1068.
[5] Bird AP. DNA methylation and the frequency of CpG in animal DNA[J]. Nucleic Acids Res,1980,8(7):1499-1504.
[6] Davegardh C, Garcia-Calzon S, Bacos K, et al. DNA methylation in the pathogenesis of type 2 diabetes in humans[J]. Mol Metab,2018,14:12-25.
[7] Fece de la Cruz F, Corcoran RB. Methylation in cell-free DNA for early cancer detection[J]. Ann Oncol,2018,29(6):1351-1353.
[8] Fransquet PD, Lacaze P, Saffery R, et al. Blood DNA methylation as a potential biomarker of dementia: A systematic review[J]. Alzheimers Dement,2018,14(1):81-103.
[9] Robertson KD. DNA methylation and human disease[J]. Nat Rev Genet,2005,6(8):597-610.
[10] Hodges E, Smith AD, Kendall J, et al. High definition profiling of mammalian DNA methylation by array capture and single molecule bisulfite sequencing[J]. Genome Res,2009,19(9):1593-1605.
[11] Edwards JR, Yarychkivska O, Boulard M, et al. DNA methylation and DNA methyltransferases[J]. Epigenetics Chromatin,2017,10:23.
[12] Chodavarapu RK, Feng S, Bernatavichute YV, et al. Relationship between nucleosome positioning and DNA methylation[J]. Nature,2010,466(7304):388-392.
[13] Hirahara K, Nakayama T. CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm[J]. Int Immunol,2016,28(4):163-171.
[14] Buckner JH. Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases[J]. Nat Rev Immunol,2010,10(12):849-859.
[15] Wang Z, Chang C, Lu Q. Epigenetics of CD4+ T cells in autoimmune diseases[J]. Curr Opin Rheumatol,2017,29(4):361-368.
[16] Ouyang H, Shi YB, Su N, et al. Abnormality and significance of interleukin-9 and CD4(+)interleukin-9(+) T-cells in peripheral blood of patients with systemic lupus erythematosus[J]. Zhonghua Yi Xue Za Zhi,2013,93(2):99-103.
[17] Singh TP, Schon MP, Wallbrecht K, et al. Involvement of IL-9 in Th17-associated inflammation and angiogenesis of psoriasis[J]. PLoS One,2013,8(1):e51752.
[18] Albanesi C. Keratinocytes in allergic skin diseases[J]. Curr Opin Allergy Clin Immunol,2010,10(5):452-456.
[19] Tokura Y. Th17 cells and skin diseases[J]. Nihon Rinsho Meneki Gakkai Kaishi,2012,35(5):388-392.
[20] Fujita H. The role of IL-22 and Th22 cells in human skin diseases[J]. J Dermatol Sci,2013,72(1):3-8.
[21] 秦思, 温炬, 郑荣昌,等.T细胞在银屑病与特应性皮炎发病机制中的研究进展[J].广东医学,2013,(7):1126-1129.
[22] Perera GK, Di Meglio P, Nestle FO. Psoriasis[J]. Annu Rev Pathol,2012,7:385-422.
[23] Lowes MA, Suarez-Farinas M, Krueger JG. Immunology of psoriasis[J]. Annu Rev Immunol,2014,32:227-255.
[24] Schakel K, Schon MP, Ghoreschi K. Pathogenesis of psoriasis[J]. Hautarzt,2016,67(6):422-431.
[25] Grayson M. Psoriasis[J]. Nature,2012,492(7429):S49.
[26] Zhang P, Zhao M, Liang G, et al. Whole-genome DNA methylation in skin lesions from patients with psoriasis vulgaris[J]. J Autoimmun,2013,41:17-24.
[27] Zhou F, Shen C, Xu J, et al. Epigenome-wide association data implicates DNA methylation-mediated genetic risk in psoriasis[J]. Clin Epigenetics,2016,8:131.
[28] Zhou F, Wang W, Shen C, et al. Epigenome-wide association analysis identified nine skin DNA methylation loci for psoriasis[J]. J Invest Dermatol,2016,136(4):779-787.
[29] Dozmorov MG, Coit P, Maksimowicz-McKinnon K, et al. Age-associated DNA methylation changes in naive CD4+ T cells suggest an evolving autoimmune epigenotype in aging T cells[J]. Epigenomics,2017,9(4):429-445.
[30] Zhao M, Qin J, Yin H, et al. Distinct epigenomes in CD4+ T cells of newborns, middle-ages and centenarians[J]. Sci Rep,2016,6:38411.
[31] Han J, Park SG, Bae JB, et al. The characteristics of genome-wide DNA methylation in naive CD4+ T cells of patients with psoriasis or atopic dermatitis[J]. Biochem Biophys Res Commun,2012,422(1):157-163.
[32] Park GT, Han J, Park SG, et al. DNA methylation analysis of CD4+ T cells in patients with psoriasis[J]. Arch Dermatol Res,2014,306(3):259-268.
[33] Gervin K, Vigeland MD, Mattingsdal M, et al. DNA methylation and gene expression changes in monozygotic twins discordant for psoriasis: identification of epigenetically dysregulated genes[J]. PLoS Genet,2012,8(1):e1002454.
[34] Ngalamika O, Liang G, Zhao M, et al. Peripheral whole blood FOXP3 TSDR methylation: a potential marker in severity assessment of autoimmune diseases and chronic infections[J]. Immunol Invest,2015,44(2):126-136.
[35] Huang L, Yang Y, Kuang Y, et al. The Impact of T cell vaccination in alleviating and regulating systemic lupus erythematosus manifestation[J]. J Immunol Res,2016,2016:5183686.
[36] Coit P, Jeffries M, Altorok N, et al. Genome-wide DNA methylation study suggests epigenetic accessibility and transcriptional poising of interferon-regulated genes in naive CD4+ T cells from lupus patients[J]. J Autoimmun,2013,43:78-84.
[37] Absher DM, Li X, Waite LL, et al. Genome-wide DNA methylation analysis of systemic lupus erythematosus reveals persistent hypomethylation of interferon genes and compositional changes to CD4+ T-cell populations[J]. PLoS Genet,2013,9(8):e1003678.
[38] Coit P, Dozmorov MG, Merrill JT, et al. Epigenetic reprogramming in naive CD4+ T cells favoring T cell activation and Non-Th1 effector T cell immune response as an early event in lupus flares[J]. Arthritis Rheumatol,2016,68(9):2200-2209.
[39] Coit P, Renauer P, Jeffries MA, et al. Renal involvement in lupus is characterized by unique DNA methylation changes in naive CD4+ T cells[J]. J Autoimmun,2015,61:29-35.
[40] Zhao M, Wang J, Liao W, et al. Increased 5-hydroxymethylcytosine in CD4(+) T cells in systemic lupus erythematosus[J]. J Autoimmun,2016,69:64-73.
[41] Zhao M, Liu S, Luo S, et al. DNA methylation and mRNA and microRNA expression of SLE CD4+ T cells correlate with disease phenotype[J]. J Autoimmun,2014,54:127-136.
[42] Alexander T, Sattler A, Templin L, et al. Foxp3+ Helios+ regulatory T cells are expanded in active systemic lupus erythematosus[J]. Ann Rheum Dis,2013,72(9):1549-1558.
[43] Konya C, Paz Z, Tsokos GC. The role of T cells in systemic lupus erythematosus: an update[J]. Curr Opin Rheumatol,2014,26(5):493-501.
[44] Lei W, Luo Y, Yan K, et al. Abnormal DNA methylation in CD4+ T cells from patients with systemic lupus erythematosus, systemic sclerosis, and dermatomyositis[J]. Scand J Rheumatol,2009,38(5):369-374.
[45] Jiang H, Xiao R, Lian X, et al. Demethylation of TNFSF7 contributes to CD70 overexpression in CD4+ T cells from patients with systemic sclerosis[J]. Clinical Immunol,2012,143(1):39-44.
[46] Wang YY, Wang Q, Sun XH, et al. DNA hypermethylation of the forkhead box protein 3 (FOXP3) promoter in CD4+ T cells of patients with systemic sclerosis[J]. Br J Dermatol,2014,171(1):39-47.
[47] Lian X, Xiao R, Hu X, et al. DNA demethylation of CD40l in CD4+ T cells from women with systemic sclerosis: a possible explanation for female susceptibility[J]. Arthritis Rheum,2012,64(7):2338-2345.
[48] Yin H, Zhao M, Wu X, et al. Hypomethylation and overexpression of CD70 (TNFSF7) in CD4+ T cells of patients with primary Sj?gren’s syndrome[J]. J Dermatol Science,2010,59(3):198-203.