368
Views
1
CrossRef citations to date
0
Altmetric
Research Article

Age-Associated DNA Methylation Changes in Naive CD4+ T Cells Suggest an Evolving Autoimmune Epigenotype in Aging T Cells

, , &
Pages 429-445 | Received 17 Oct 2016, Accepted 21 Dec 2016, Published online: 21 Mar 2017

References

  • Pilling LC , AtkinsJL , BowmanKet al. Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants . Aging (Albany NY) ( 2016 ).
  • Brooks–Wilson AR . Genetics of healthy aging and longevity . Hum. Genet.132 ( 12 ), 1323 – 1338 ( 2013 ).
  • Christensen K , JohnsonTE , VaupelJW . The quest for genetic determinants of human longevity: challenges and insights . Nat. Rev. Genet.7 ( 6 ), 436 – 448 ( 2006 ).
  • Coolen MW , StathamAL , QuWet al. Impact of the genome on the epigenome is manifested in DNA methylation patterns of imprinted regions in monozygotic and dizygotic twins . PLoS ONE6 ( 10 ), e25590 ( 2011 ).
  • Gertz J , VarleyKE , ReddyTEet al. Analysis of DNA methylation in a three-generation family reveals widespread genetic influence on epigenetic regulation . PLoS Genet.7 ( 8 ), e1002228 ( 2011 ).
  • Rodriguez–Paredes M , EstellerM . Cancer epigenetics reaches mainstream oncology . Nat. Med.17 ( 3 ), 330 – 339 ( 2011 ).
  • Johnson AA , AkmanK , CalimportSR , WuttkeD , StolzingA , De MagalhaesJP . The role of DNA methylation in aging, rejuvenation, and age-related disease . Rejuvenation Res.15 ( 5 ), 483 – 494 ( 2012 ).
  • Lopez–Otin C , BlascoMA , PartridgeL , SerranoM , KroemerG . The hallmarks of aging . Cell153 ( 6 ), 1194 – 1217 ( 2013 ).
  • Richardson BC . Role of DNA methylation in the regulation of cell function: autoimmunity, aging and cancer . J. Nutr.132 ( Suppl. 8 ), S2401 – S2405 ( 2002 ).
  • Teschendorff AE , MenonU , Gentry–MaharajAet al. Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer . Genome Res.20 ( 4 ), 440 – 446 ( 2010 ).
  • Hannum G , GuinneyJ , ZhaoLet al. Genome-wide methylation profiles reveal quantitative views of human aging rates . Mol. Cell49 ( 2 ), 359 – 367 ( 2013 ).
  • Horvath S . DNA methylation age of human tissues and cell types . Genome Biol.14 ( 10 ), R115 ( 2013 ).
  • Alisch RS , BarwickBG , ChopraPet al. Age-associated DNA methylation in pediatric populations . Genome Res.22 ( 4 ), 623 – 632 ( 2012 ).
  • Marttila S , KananenL , HayrynenSet al. Ageing-associated changes in the human DNA methylome: genomic locations and effects on gene expression . BMC Genomics16 , 179 ( 2015 ).
  • Mcclay JL , AbergKA , ClarkSLet al. A methylome-wide study of aging using massively parallel sequencing of the methyl-CpG-enriched genomic fraction from blood in over 700 subjects . Hum. Mol. Genet.23 ( 5 ), 1175 – 1185 ( 2014 ).
  • Rakyan VK , DownTA , MaslauSet al. Human aging–associated DNA hypermethylation occurs preferentially at bivalent chromatin domains . Genome Res.20 ( 4 ), 434 – 439 ( 2010 ).
  • Dozmorov MG . Polycomb repressive complex 2 epigenomic signature defines age-associated hypermethylation and gene expression changes . Epigenetics10 ( 6 ), 484 – 495 ( 2015 ).
  • Steegenga WT , BoekschotenMV , LuteCet al. Genome-wide age-related changes in DNA methylation and gene expression in human PBMCs . Age (Dordr.)36 ( 3 ), 9648 ( 2014 ).
  • Weidner CI , LinQ , KochCMet al. Aging of blood can be tracked by DNA methylation changes at just three CpG sites . Genome Biol.15 ( 2 ), R24 ( 2014 ).
  • Teschendorff AE , MarabitaF , LechnerMet al. A beta-mixture quantile normalization method for correcting probe design bias in Illumina Infinium 450 k DNA methylation data . Bioinformatics29 ( 2 ), 189 – 196 ( 2013 ).
  • Koch CM , WagnerW . Epigenetic-aging-signature to determine age in different tissues . Aging (Albany NY)3 ( 10 ), 1018 – 1027 ( 2011 ).
  • Jaffe AE , IrizarryRA . Accounting for cellular heterogeneity is critical in epigenome-wide association studies . Genome Biol.15 ( 2 ), R31 ( 2014 ).
  • Moro-García MA , Alonso-AriasR , López-LarreaC . When aging reaches CD4+ T-cells: phenotypic and functional changes . Front. Immunol.4 , 107 ( 2013 ).
  • Jeffries MA , SawalhaAH . Autoimmune disease in the epigenetic era: how has epigenetics changed our understanding of disease and how can we expect the field to evolve?Expert Rev. Clin. Immunol.11 ( 1 ), 45 – 58 ( 2015 ).
  • Sawalha AH , HarleyJB . Antinuclear autoantibodies in systemic lupus erythematosus . Curr. Opin. Rheumatol.16 ( 5 ), 534 – 540 ( 2004 ).
  • Zhang Z , DengC , LuQ , RichardsonB . Age-dependent DNA methylation changes in the ITGAL (CD11a) promoter . Mech. Ageing Dev.123 ( 9 ), 1257 – 1268 ( 2002 ).
  • Coit P , JeffriesM , AltorokNet 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. Autoimmun.43 , 78 – 84 ( 2013 ).
  • Coit P , OgnenovskiM , GensterblumE , Maksimowicz–MckinnonK , WrenJD , SawalhaAH . Ethnicity-specific epigenetic variation in naive CD4+ T cells and the susceptibility to autoimmunity . Epigenetics Chromatin8 , 49 ( 2015 ).
  • Chen YA , LemireM , ChoufaniSet al. Discovery of cross-reactive probes and polymorphic CpGs in the Illumina Infinium HumanMethylation450 microarray . Epigenetics8 ( 2 ), 203 – 209 ( 2013 ).
  • Ferrari S , Cribari-NetoF . Beta regression for modelling rates and proportions . J. Appl. Stat.31 ( 7 ), 799 – 815 ( 2004 ).
  • Cribari-Neto F , ZeileisA . Beta regression in R . J. Stat. Softw.34 ( 2 ), 1 – 24 ( 2010 ).
  • Du P , KibbeWA , LinSM . lumi: a pipeline for processing Illumina microarray . Bioinformatics24 ( 13 ), 1547 – 1548 ( 2008 ).
  • Dozmorov MG , CaraLR , GilesCB , WrenJD . GenomeRunner web server: regulatory similarity and differences define the functional impact of SNP sets . Bioinformatics32 ( 15 ), 2256 – 2263 ( 2016 ).
  • Rosenbloom KR , SloanCA , MalladiVSet al. ENCODE data in the UCSC genome browser: year 5 update . Nucleic Acids Res.41 , D56 – D63 ( 2013 ).
  • Harrow JL , StewardCA , FrankishAet al. The vertebrate genome annotation browser 10 years on . Nucleic Acids Res.42 , D771 – D779 ( 2014 ).
  • Cooper GM , StoneEA , AsimenosGet al. Distribution and intensity of constraint in mammalian genomic sequence . Genome Res.15 ( 7 ), 901 – 913 ( 2005 ).
  • Wu H , CaffoB , JaffeeHA , IrizarryRA , FeinbergAP . Redefining CpG islands using hidden Markov models . Biostatistics11 ( 3 ), 499 – 514 ( 2010 ).
  • Andersson R , GebhardC , Miguel–EscaladaIet al. An atlas of active enhancers across human cell types and tissues . Nature507 ( 7493 ), 455 – 461 ( 2014 ).
  • Roadmap Epigenomics C , KundajeA , MeulemanWet al. Integrative analysis of 111 reference human epigenomes . Nature518 ( 7539 ), 317 – 330 ( 2015 ).
  • Kanehisa M , GotoS . KEGG: Kyoto encyclopedia of genes and genomes . Nucleic Acids Res.28 ( 1 ), 27 – 30 ( 2000 ).
  • Slieker RC , van ItersonM , LuijkRet al. Age-related accrual of methylomic variability is linked to fundamental ageing mechanisms . Genome Biol.17 ( 1 ), 191 ( 2016 ).
  • Reynolds LM , TaylorJR , DingJet al. Age-related variations in the methylome associated with gene expression in human monocytes and T cells . Nat. Commun.5 , 5366 ( 2014 ).
  • Heyn H , LiN , FerreiraHJet al. Distinct DNA methylomes of newborns and centenarians . Proc. Natl Acad. Sci. USA109 ( 26 ), 10522 – 10527 ( 2012 ).
  • Wilson VL , JonesPA . DNA methylation decreases in aging but not in immortal cells . Science220 ( 4601 ), 1055 – 1057 ( 1983 ).
  • Florath I , ButterbachK , MullerH , Bewerunge-HudlerM , BrennerH . Cross-sectional and longitudinal changes in DNA methylation with age: an epigenome-wide analysis revealing over 60 novel age-associated CpG sites . Hum. Mol. Genet.23 ( 5 ), 1186 – 1201 ( 2014 ).
  • Bernstein BE , MikkelsenTS , XieXet al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells . Cell125 ( 2 ), 315 – 326 ( 2006 ).
  • Schraml BU , HildnerK , IseWet al. The AP-1 transcription factor Batf controls T(H)17 differentiation . Nature460 ( 7253 ), 405 – 409 ( 2009 ).
  • Dovat S . Ikaros: the enhancer makes the difference . Blood122 ( 18 ), 3091 – 3092 ( 2013 ).
  • Yoshida T , LandhuisE , DoseMet al. Transcriptional regulation of the Ikzf1 locus . Blood122 ( 18 ), 3149 – 3159 ( 2013 ).
  • Yu Y , WangJ , KhaledWet al. Bcl11a is essential for lymphoid development and negatively regulates p53 . J. Exp. Med.209 ( 13 ), 2467 – 2483 ( 2012 ).
  • Liu W , TanasaB , TyurinaOVet al. PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression . Nature466 ( 7305 ), 508 – 512 ( 2010 ).
  • Li X , LiuL , YangSet al. Histone demethylase KDM5B is a key regulator of genome stability . Proc. Natl Acad. Sci. USA111 ( 19 ), 7096 – 7101 ( 2014 ).
  • Creyghton MP , ChengAW , WelsteadGGet al. Histone H3K27ac separates active from poised enhancers and predicts developmental state . Proc. Natl Acad. Sci. USA107 ( 50 ), 21931 – 21936 ( 2010 ).
  • López-Otín C , BlascoMA , PartridgeL , SerranoM , KroemerG . The hallmarks of aging . Cell153 ( 6 ), 1194 – 1217 ( 2013 ).
  • Zampieri M , CiccaroneF , CalabreseR , FranceschiC , BürkleA , CaiafaP . Reconfiguration of DNA methylation in aging . Mech. Ageing Dev.151 , 60 – 70 ( 2015 ).
  • Deaton AM , BirdA . CpG islands and the regulation of transcription . Genes Dev.25 ( 10 ), 1010 – 1022 ( 2011 ).
  • Coit P , DozmorovMG , MerrillJTet 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 . Arthritis Rheumatol.68 ( 9 ), 2200 – 2209 ( 2016 ).
  • Fransen E , BonneuxS , CorneveauxJJet al. Genome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairment . Eur. J. Hum. Genet.23 ( 1 ), 110 – 115 ( 2015 ).
  • Lunetta KL , D’agostinoRB , KarasikDet al. Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study . BMC Med. Genet.8 ( Suppl. 1 ), S13 ( 2007 ).
  • Walter S , AtzmonG , DemerathEWet al. A genome-wide association study of aging . Neurobiol. Aging32 ( 11 ), 2109.e2115 – 2109.e2128 ( 2011 ).
  • Kamboh MI , BarmadaMM , DemirciFYet al. Genome-wide association analysis of age-at-onset in Alzheimer’s disease . Mol. Psychiatry17 ( 12 ), 1340 – 1346 ( 2012 ).
  • Xie T , DengL , MeiPet al. Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations . Neurobiol. Aging35 ( 7 ), 1778.e1779 – 1778.e1723 ( 2014 ).
  • Perez-Andreu V , RobertsKG , XuHet al. A genome-wide association study of susceptibility to acute lymphoblastic leukemia in adolescents and young adults . Blood125 ( 4 ), 680 – 686 ( 2015 ).
  • Baranzini SE , WangJ , GibsonRAet al. Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis . Hum. Mol. Genet.18 ( 4 ), 767 – 778 ( 2009 ).
  • Festen EaM , GoyetteP , GreenTet al. A meta-analysis of genome-wide association scans identifies IL18RAP, PTPN2, TAGAP, and PUS10 as shared risk loci for Crohn’s disease and celiac disease . PLoS Genet.7 ( 1 ), e1001283 ( 2011 ).
  • Garagnani P , BacaliniMG , PirazziniCet al. Methylation of ELOVL2 gene as a new epigenetic marker of age . Aging Cell11 ( 6 ), 1132 – 1134 ( 2012 ).
  • Chiurchiù V , LeutiA , DalliJet al. Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses . Sci. Transl. Med.8 ( 353 ), 353ra111 – 353ra111 ( 2016 ).
  • Dashti M , PeppelenboschMP , RezaeeF . Hedgehog signalling as an antagonist of ageing and its associated diseases . Bioessays34 ( 10 ), 849 – 856 ( 2012 ).
  • Gorelik G , FangJY , WuA , SawalhaAH , RichardsonB . Impaired T cell protein kinase C delta activation decreases ERK pathway signaling in idiopathic and hydralazine-induced lupus . J. Immunol.179 ( 8 ), 5553 – 5563 ( 2007 ).
  • Lu Q , KaplanM , RayDet al. Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupus erythematosus . Arthritis Rheum.46 ( 5 ), 1282 – 1291 ( 2002 ).
  • Lu Q , WuA , TesmerL , RayD , YousifN , RichardsonB . Demethylation of CD40LG on the inactive X in T cells from women with lupus . J. Immunol.179 ( 9 ), 6352 – 6358 ( 2007 ).
  • Perl A . mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging . Ann. NY. Acad. Sci.1346 ( 1 ), 33 – 44 ( 2015 ).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.