130
Views
0
CrossRef citations to date
0
Altmetric
ORIGINAL RESEARCH

Integrated DNA Methylation and Transcriptomics Analyses of Lacrimal Glands Identify the Potential Genes Implicated in the Development of Sjögren’s Syndrome-Related Dry Eye

ORCID Icon, , , , &
Pages 5697-5714 | Received 15 Sep 2023, Accepted 21 Nov 2023, Published online: 29 Nov 2023

References

  • Imgenberg-Kreuz J, Sandling JK, Nordmark G. Epigenetic alterations in primary Sjögren’s syndrome - an overview. Clin Immunol. 2018;196:12–20. doi:10.1016/j.clim.2018.04.004
  • Choudhry HS, Hosseini S, Choudhry HS, Fatahzadeh M, Khianey R, Dastjerdi MH. Updates in diagnostics, treatments, and correlations between oral and ocular manifestations of Sjogren’s syndrome. Ocul Surf. 2022;26:75–87. doi:10.1016/j.jtos.2022.08.001
  • Foulks GN, Forstot SL, Donshik PC, et al. Clinical guidelines for management of dry eye associated with Sjögren disease. Ocul Surf. 2015;13(2):118–132. doi:10.1016/j.jtos.2014.12.001
  • Lafontaine N, Wilson SG, Walsh JP. DNA Methylation in Autoimmune Thyroid Disease. J Clin Endocrinol Metab. 2023;108(3):604–613. doi:10.1210/clinem/dgac664
  • Qiu Y, Zhu Y, Yu H, Zhou C, Kijlstra A, Yang P. Dynamic DNA Methylation Changes of Tbx21 and Rorc during Experimental Autoimmune Uveitis in Mice. Mediators Inflamm. 2018;2018:9129163. doi:10.1155/2018/9129163
  • Cheng L, Li H, Zhan H, et al. Alterations of m6A RNA methylation regulators contribute to autophagy and immune infiltration in primary Sjögren’s syndrome. Front Immunol. 2022;13:949206. doi:10.3389/fimmu.2022.949206
  • Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013;38(1):23–38. doi:10.1038/npp.2012.112
  • Chuang TJ, Chen FC. DNA methylation is associated with an increased level of conservation at nondegenerate nucleotides in mammals. Mol Biol Evol. 2014;31(2):387–396. doi:10.1093/molbev/mst208
  • Zhao F, Wu W, Wei Q, et al. Exogenous adrenocorticotropic hormone affects genome-wide DNA methylation and transcriptome of corpus luteum in sows. FASEB j. 2019;33(3):3264–3278. doi:10.1096/fj.201801081RRR
  • Du Y, Li J, Wu J, Zeng F, He C. Exploration of the pathogenesis of Sjögren’s syndrome via DNA methylation and transcriptome analyses. Clin Rheumatol. 2022;41(9):2765–2777. doi:10.1007/s10067-022-06200-4
  • Yu X, Liang G, Yin H, et al. DNA hypermethylation leads to lower FOXP3 expression in CD4+ T cells of patients with primary Sjögren’s syndrome. Clin Immunol. 2013;148(2):254–257. doi:10.1016/j.clim.2013.05.005
  • Konsta OD, Le Dantec C, Charras A, et al. Defective DNA methylation in salivary gland epithelial acini from patients with Sjögren’s syndrome is associated with SSB gene expression, anti-SSB/LA detection, and lymphocyte infiltration. J Autoimmun. 2016;68:30–38. doi:10.1016/j.jaut.2015.12.002
  • Chi C, Solomon O, Shiboski C, et al. Identification of Sjögren’s syndrome patient subgroups by clustering of labial salivary gland DNA methylation profiles. PLoS One. 2023;18(3):e0281891. doi:10.1371/journal.pone.0281891
  • Chiorini JA, Cihakova D, Ouellette CE, Caturegli P. Sjögren syndrome: advances in the pathogenesis from animal models. J Autoimmun. 2009;33(3–4):190–196. doi:10.1016/j.jaut.2009.09.009
  • Shin S, Yoon SG, Kim M, et al. The Effect of Mesenchymal Stem Cells on Dry Eye in Sjogren Syndrome Mouse Model. Int J Mol Sci. 2023;24(2):1039. doi:10.3390/ijms24021039
  • Guo X, Dang W, Li N, et al. PPAR-α Agonist Fenofibrate Ameliorates Sjögren Syndrome-Like Dacryoadenitis by Modulating Th1/Th17 and Treg Cell Responses in NOD Mice. Invest Ophthalmol Vis Sci. 2022;63(6):12. doi:10.1167/iovs.63.6.12
  • Masli S, Dartt DA. Mouse Models of Sjögren’s Syndrome with Ocular Surface Disease. Int J Mol Sci. 2020;21(23):9112. doi:10.3390/ijms21239112
  • Schenke-Layland K, Xie J, Angelis E, et al. Increased degradation of extracellular matrix structures of lacrimal glands implicated in the pathogenesis of Sjögren’s syndrome. Matrix Biol. 2008;27(1):53–66. doi:10.1016/j.matbio.2007.07.005
  • Robinson CP, Cornelius J, Bounous DI, Yamamoto H, Humphreys-Beher MG, Peck AB. Infiltrating lymphocyte populations and cytokine production in the salivary and lacrimal glands of autoimmune NOD mice. Adv Exp Med Biol. 1998;438:493–497. doi:10.1007/978-1-4615-5359-5_68
  • Yamano S, Atkinson JC, Baum BJ, Fox PC. Salivary gland cytokine expression in NOD and normal BALB/c mice. Clin Immunol. 1999;92(3):265–275. doi:10.1006/clim.1999.4759
  • Guo H, Ju Y, Choi M, et al. Supra-lacrimal protein-based carriers for cyclosporine A reduce Th17-mediated autoimmunity in murine model of Sjögren’s syndrome. Biomaterials. 2022;283:121441. doi:10.1016/j.biomaterials.2022.121441
  • Ohno Y, Satoh K, Shitara A, Into T, Kashimata M. Arginase 1 is involved in lacrimal hyposecretion in male NOD mice, a model of Sjögren’s syndrome, regardless of dacryoadenitis status. J Physiol. 2020;598(21):4907–4925. doi:10.1113/jp280090
  • Xiao X, Luo P, Zhao H, et al. Amniotic membrane extract ameliorates benzalkonium chloride-induced dry eye in a murine model. Exp Eye Res. 2013;115:31–40. doi:10.1016/j.exer.2013.06.005
  • Debreceni IL, Chimenti MS, Serreze DV, Geurts AM, Chen YG, Lieberman SM. Toll-Like Receptor 7 Is Required for Lacrimal Gland Autoimmunity and Type 1 Diabetes Development in Male Nonobese Diabetic Mice. Int J Mol Sci. 2020;21(24):9478. doi:10.3390/ijms21249478
  • Allred MG, Chimenti MS, Ciecko AE, Chen YG, Lieberman SM. Characterization of Type I Interferon-Associated Chemokines and Cytokines in Lacrimal Glands of Nonobese Diabetic Mice. Int J Mol Sci. 2021;22(7):67. doi:10.3390/ijms22073767
  • Meng M, Li X, Ge H, et al. Noninvasive prenatal testing for autosomal recessive conditions by maternal plasma sequencing in a case of congenital deafness. Genet Med. 2014;16(12):972–976. doi:10.1038/gim.2014.51
  • Xi Y, Li W. BSMAP: whole genome bisulfite sequence MAPping program. BMC Bioinf. 2009;10:232. doi:10.1186/1471-2105-10-232
  • Akalin A, Kormaksson M, Li S, et al. methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles. Genome Biol. 2012;13(10):R87. doi:10.1186/gb-2012-13-10-r87
  • Jühling F, Kretzmer H, Bernhart SH, Otto C, Stadler PF, Hoffmann S. metilene: fast and sensitive calling of differentially methylated regions from bisulfite sequencing data. Genome Res. 2016;26(2):256–262. doi:10.1101/gr.196394.115
  • Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114–2120. doi:10.1093/bioinformatics/btu170
  • Kim D, Paggi JM, Park C, Bennett C, Salzberg SL. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat Biotechnol. 2019;37(8):907–915. doi:10.1038/s41587-019-0201-4
  • Pertea M, Kim D, Pertea GM, Leek JT, Salzberg SL. Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown. Nat Protoc. 2016;11(9):1650–1667. doi:10.1038/nprot.2016.095
  • Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. doi:10.1186/s13059-014-0550-8
  • Wu T, Hu E, Xu S, et al. clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innovation. 2021;2(3):100141. doi:10.1016/j.xinn.2021.100141
  • Huang da W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37(1):1–13. doi:10.1093/nar/gkn923
  • Takahashi M, Ishimaru N, Yanagi K, Haneji N, Saito I, Hayashi Y. High incidence of autoimmune dacryoadenitis in male non-obese diabetic (NOD) mice depending on sex steroid. Clin Exp Immunol. 1997;109(3):555–561. doi:10.1046/j.1365-2249.1997.4691368.x
  • Hunger RE, Carnaud C, Vogt I, Mueller C. Male gonadal environment paradoxically promotes dacryoadenitis in nonobese diabetic mice. J Clin Invest. 1998;101(6):1300–1309. doi:10.1172/jci1230
  • Imgenberg-Kreuz J, Almlöf JC, Leonard D, et al. Shared and Unique Patterns of DNA Methylation in Systemic Lupus Erythematosus and Primary Sjögren’s Syndrome. Front Immunol. 2019;10:1686. doi:10.3389/fimmu.2019.01686
  • Biro M, Munoz MA, Weninger W. Targeting Rho-GTPases in immune cell migration and inflammation. Br J Pharmacol. 2014;171(24):5491–5506. doi:10.1111/bph.12658
  • Peck AB, Nguyen CQ, Ambrus JL. Upregulated Chemokine and Rho-GTPase Genes Define Immune Cell Emigration into Salivary Glands of Sjögren’s Syndrome-Susceptible C57BL/6.NOD-Aec1Aec2 Mice. Int J Mol Sci. 2021;22(13):7176. doi:10.3390/ijms22137176
  • Peck AB, Nguyen CQ, Ambrus JL Jr. A MZB Cell Activation Profile Present in the Lacrimal Glands of Sjögren’s Syndrome-Susceptible C57BL/6.NOD-Aec1Aec2 Mice Defined by Global RNA Transcriptomic Analyses. Int J Mol Sci. 2022;23(11):6160. doi:10.3390/ijms23116106
  • Han Y, Guo S, Li Y, et al. Berberine ameliorate inflammation and apoptosis via modulating PI3K/AKT/NFκB and MAPK pathway on dry eye. Phytomedicine. 2023;121:155081. doi:10.1016/j.phymed.2023.155081
  • Chen YC, Lin IC, Su MC, et al. Autophagy impairment in patients with obstructive sleep apnea modulates intermittent hypoxia-induced oxidative stress and cell apoptosis via hypermethylation of the ATG5 gene promoter region. Eur J Med Res. 2023;28(1):82. doi:10.1186/s40001-023-01051-4
  • Gasque Schoof CR, Izzotti A, Jasiulionis MG, Vasques Ldos R. The Roles of miR-26, miR-29, and miR-203 in the Silencing of the Epigenetic Machinery during Melanocyte Transformation. Biomed Res Int. 2015;2015:634749. doi:10.1155/2015/634749
  • Wang X, Bhandari RK. DNA methylation dynamics during epigenetic reprogramming of medaka embryo. Epigenetics. 2019;14(6):611–622. doi:10.1080/15592294.2019.1605816
  • Zhang Z, Wang J, Shi F, et al. Genome-wide alternation and effect of DNA methylation in the impairments of steroidogenesis and spermatogenesis after PM(2.5) exposure. Environ Int. 2022;169:107544. doi:10.1016/j.envint.2022.107544
  • Thorlacius GE, Björk A, Wahren-Herlenius M. Genetics and epigenetics of primary Sjögren syndrome: implications for future therapies. Nat Rev Rheumatol. 2023;19(5):288–306. doi:10.1038/s41584-023-00932-6
  • Li P, Han M, Zhao X, Ren G, Mei S, Zhong C. Abnormal Epigenetic Regulations in the Immunocytes of Sjögren’s Syndrome Patients and Therapeutic Potentials. Cells. 2022;11(11):767. doi:10.3390/cells11111767
  • Slotkin RK, Martienssen R. Transposable elements and the epigenetic regulation of the genome. Nat Rev Genet. 2007;8(4):272–285. doi:10.1038/nrg2072
  • Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012;13(7):484–492. doi:10.1038/nrg3230
  • de Oliveira DT, de Paiva NCN, Carneiro CM, Guerra-Sá R. Dynamic changes in hepatic DNA methylation during the development of nonalcoholic fatty liver disease induced by a high-sugar diet. J Physiol Biochem. 2022;78(4):763–775. doi:10.1007/s13105-022-00900-w
  • Komatsu Y, Waku T, Iwasaki N, Ono W, Yamaguchi C, Yanagisawa J. Global analysis of DNA methylation in early-stage liver fibrosis. BMC Med Genomics. 2012;5:5. doi:10.1186/1755-8794-5-5
  • Rui J, Deng S, Lebastchi J, Clark PL, Usmani-Brown S, Herold KC. Methylation of insulin DNA in response to proinflammatory cytokines during the progression of autoimmune diabetes in NOD mice. Diabetologia. 2016;59(5):1021–1029. doi:10.1007/s00125-016-3897-4
  • Cole MB, Quach H, Quach D, et al. Epigenetic Signatures of Salivary Gland Inflammation in Sjögren’s Syndrome. Arthritis Rheumatol. 2016;68(12):2936–2944. doi:10.1002/art.39792
  • Imgenberg-Kreuz J, Sandling JK, Almlöf JC, et al. Genome-wide DNA methylation analysis in multiple tissues in primary Sjögren’s syndrome reveals regulatory effects at interferon-induced genes. Ann Rheum Dis. 2016;75(11):2029–2036. doi:10.1136/annrheumdis-2015-208659
  • Meng Z, Edman MC, Hsueh PY, et al. Imbalanced Rab3D versus Rab27 increases cathepsin S secretion from lacrimal acini in a mouse model of Sjögren’s Syndrome. Am J Physiol Cell Physiol. 2016;310(11):C942–54. doi:10.1152/ajpcell.00275.2015
  • Fu R, Edman MC, Hamm-Alvarez SF. Rab27a Contributes to Cathepsin S Secretion in Lacrimal Gland Acinar Cells. Int J Mol Sci. 2021;22(4):1630. doi:10.3390/ijms22041630
  • Ogawa Y, Shimizu E, Tsubota K. Interferons and Dry Eye in Sjögren’s Syndrome. Int J Mol Sci. 2018;19(11):3548. doi:10.3390/ijms19113548
  • Ogawa Y, Takeuchi T, Tsubota K. Autoimmune Epithelitis and Chronic Inflammation in Sjögren’s Syndrome-Related Dry Eye Disease. Int J Mol Sci. 2021;22(21):11820. doi:10.3390/ijms222111820
  • Gupta S, Li D, Ostrov DA, Nguyen CQ. Blocking IAg(7) class II major histocompatibility complex by drug-like small molecules alleviated Sjögren’s syndrome in NOD mice. Life Sci. 2022;288:120182. doi:10.1016/j.lfs.2021.120182
  • Abdulahad WH, Kroese FG, Vissink A, Bootsma H. Immune regulation and B-cell depletion therapy in patients with primary Sjögren’s syndrome. J Autoimmun. 2012;39(1–2):103–111. doi:10.1016/j.jaut.2012.01.009
  • Karabiyik A, Peck AB, Nguyen CQ. The important role of T cells and receptor expression in Sjögren’s syndrome. Scand J Immunol. 2013;78(2):157–166. doi:10.1111/sji.12079
  • Emamian ES, Leon JM, Lessard CJ, et al. Peripheral blood gene expression profiling in Sjögren’s syndrome. Genes Immun. 2009;10(4):285–296. doi:10.1038/gene.2009.20
  • Lin X, Rui K, Deng J, et al. Th17 cells play a critical role in the development of experimental Sjögren’s syndrome. Ann Rheum Dis. 2015;74(6):1302–1310. doi:10.1136/annrheumdis-2013-204584
  • Xiao F, Rui K, Han M, et al. Artesunate suppresses Th17 response via inhibiting IRF4-mediated glycolysis and ameliorates Sjogren’s syndrome. Signal Transduct Target Ther. 2022;7(1):274. doi:10.1038/s41392-022-01103-x
  • Zhang Y, Zhao M, Sawalha AH, Richardson B, Lu Q. Impaired DNA methylation and its mechanisms in CD4(+)T cells of systemic lupus erythematosus. J Autoimmun. 2013;41:92–99. doi:10.1016/j.jaut.2013.01.005
  • Luo Y, Li Y, Su Y, et al. Abnormal DNA methylation in T cells from patients with subacute cutaneous lupus erythematosus. Br J Dermatol. 2008;159(4):827–833. doi:10.1111/j.1365-2133.2008.08758.x
  • Takahashi M, Mimura Y, Hayashi Y. Role of the ICAM-1/LFA-1 pathway during the development of autoimmune dacryoadenitis in an animal model for Sjögren’s syndrome. Pathobiology. 1996;64(5):269–274. doi:10.1159/000164058
  • Gao J, Morgan G, Tieu D, et al. ICAM-1 expression predisposes ocular tissues to immune-based inflammation in dry eye patients and Sjögrens syndrome-like MRL/lpr mice. Exp Eye Res. 2004;78(4):823–835. doi:10.1016/j.exer.2003.10.024
  • Paton DM. Lifitegrast: first LFA-1/ICAM-1 antagonist for treatment of dry eye disease. Drugs Today. 2016;52(9):485–493. doi:10.1358/dot.2016.52.9.2542066
  • Holland EJ, Luchs J, Karpecki PM, et al. Lifitegrast for the Treatment of Dry Eye Disease: results of a Phase III, Randomized, Double-Masked, Placebo-Controlled Trial (OPUS-3). Ophthalmology. 2017;124(1):53–60. doi:10.1016/j.ophtha.2016.09.025
  • Du G, Du W, An Y, et al. Design, synthesis, and LFA-1/ICAM-1 antagonist activity evaluation of Lifitegrast analogues. Med Chem Res. 2022;31(4):555–579. doi:10.1007/s00044-022-02851-9
  • Xu WD, Pan HF, Ye DQ, Xu Y. Targeting IRF4 in autoimmune diseases. Autoimmun Rev. 2012;11(12):918–924. doi:10.1016/j.autrev.2012.08.011
  • Gong YZ, Nititham J, Taylor K, et al. Differentiation of follicular helper T cells by salivary gland epithelial cells in primary Sjögren’s syndrome. J Autoimmun. 2014;51:57–66. doi:10.1016/j.jaut.2013.11.003
  • Tybulewicz VL. Vav-family proteins in T-cell signalling. Curr Opin Immunol. 2005;17(3):267–274. doi:10.1016/j.coi.2005.04.003