Skip to main content

Advertisement

SpringerLink
Log in

Epigenetic Changes During Food-Specific Immunotherapy

  • Immunotherapy and Immunomodulators (B Vickery, Section Editor)
  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The prevalence and severity of IgE-mediated food allergy has increased dramatically over the last 15 years and is becoming a global health problem. Multiple lines of evidence suggest that epigenetic modifications of the genome resulting from gene-environment interactions have a key role in the increased prevalence of atopic disease. In this review, we describe the recent evidence suggesting how epigenetic changes mediate susceptibility to food allergies, and discuss how immunotherapy (IT) may reverse these effects. We discuss the areas of the epigenome as yet unexplored in terms of food allergy and IT such as histone modification and chromatin accessibility, and new techniques that may be utilized in future studies.

Recent Findings

Recent findings provide strong evidence that DNA methylation of certain promoter regions such as Forkhead box protein 3 is associated with clinical reactivity, and further, can be changed during IT treatment. Reports on other epigenetic changes are limited but also show evidence of significant change based on both disease status and treatment.

Summary

In comparison to epigenetic studies focusing on asthma and allergic rhinitis, food allergy remains understudied. However, within the next decade, it is likely that epigenetic modifications may be used as biomarkers to aid in diagnosis and treatment of food-allergic patients. DNA methylation at specific loci has shown associations between food challenge outcomes, successful desensitization treatment, and overall phenotype compared to healthy controls.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been noted as: • Of importance •• Of great importance

  1. Branum AM, Lukacs SL. Food allergy among children in the United States. Pediatrics. 2009;124(6):1549–55.

    Article  PubMed  Google Scholar 

  2. Sicherer SH, Sampson HA. Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol. 2014;133(2):291-307; quiz 8.

  3. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16(1):6–21.

    Article  CAS  PubMed  Google Scholar 

  4. Bird AP. CpG-rich islands and the function of DNA methylation. Nature. 1986;321(6067):209–13.

    Article  CAS  PubMed  Google Scholar 

  5. Song F, Smith JF, Kimura MT, Morrow AD, Matsuyama T, Nagase H, et al. Association of tissue-specific differentially methylated regions (TDMs) with differential gene expression. Proc Natl Acad Sci U S A. 2005;102(9):3336–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Saxonov S, Berg P, Brutlag DL. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci U S A. 2006;103(5):1412–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Deaton AM, Bird A. CpG islands and the regulation of transcription. Genes Dev. 2011;25(10):1010–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Robertson KD. DNA methylation and human disease. Nat Rev Genet. 2005;6(8):597–610.

    Article  CAS  PubMed  Google Scholar 

  9. Drong AW, Nicholson G, Hedman AK, Meduri E, Grundberg E, Small KS, et al. The presence of methylation quantitative trait loci indicates a direct genetic influence on the level of DNA methylation in adipose tissue. PLoS One. 2013;8(2):e55923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Liu Y, Li X, Aryee MJ, Ekstrom TJ, Padyukov L, Klareskog L, et al. GeMes, clusters of DNA methylation under genetic control, can inform genetic and epigenetic analysis of disease. Am J Hum Genet. 2014;94(4):485–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Greer FR, Sicherer SH, Burks AW. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics. 2008;121(1):183–91.

    Article  PubMed  Google Scholar 

  12. Du Toit G, Katz Y, Sasieni P, Mesher D, Maleki SJ, Fisher HR, et al. Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J Allergy Clin Immunol. 2008;122(5):984–91.

    Article  PubMed  Google Scholar 

  13. •• Du Toit G, Roberts G, Sayre PH, Bahnson HT, Radulovic S, Santos AF, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372(9):803–13. The LEAP study gave strong evidence that early exposure to an allergen is preventative. In a randomized study of 640 infants (average age = 7.8mo) who were likely to develop peanut allergy, 13.7% of children who avoided peanut were allergic to peanuts at 60 months of age compared to 1.9% of the consumption group. This helps support the theory that environmental queues are critical to the development of allergy.

    Article  PubMed  PubMed Central  Google Scholar 

  14. du Toit DF, Lambrechts AV, Stark H, Warren BL. Long-term results of stent graft treatment of subclavian artery injuries: management of choice for stable patients? J Vasc Surg. 2008;47(4):739–43.

    Article  PubMed  Google Scholar 

  15. Koplin JJ, Osborne NJ, Wake M, Martin PE, Gurrin LC, Robinson MN, et al. Can early introduction of egg prevent egg allergy in infants? A population-based study. J Allergy Clin Immunol. 2010;126(4):807–13.

    Article  PubMed  Google Scholar 

  16. Palmer DJ, Metcalfe J, Makrides M, Gold MS, Quinn P, West CE, et al. Early regular egg exposure in infants with eczema: a randomized controlled trial. J Allergy Clin Immunol. 2013;132(2):387–92 e1.

    Article  PubMed  Google Scholar 

  17. Joseph CL, Ownby DR, Havstad SL, Woodcroft KJ, Wegienka G, MacKechnie H, et al. Early complementary feeding and risk of food sensitization in a birth cohort. J Allergy Clin Immunol. 2011;127(5):1203–10 e5.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Nwaru BI, Erkkola M, Ahonen S, Kaila M, Haapala AM, Kronberg-Kippila C, et al. Age at the introduction of solid foods during the first year and allergic sensitization at age 5 years. Pediatrics. 2010;125(1):50–9.

    Article  PubMed  Google Scholar 

  19. Katz Y, Rajuan N, Goldberg MR, Eisenberg E, Heyman E, Cohen A, et al. Early exposure to cow’s milk protein is protective against IgE-mediated cow’s milk protein allergy. J Allergy Clin Immunol. 2010;126(1):77–82 e1.

    Article  CAS  PubMed  Google Scholar 

  20. Furuhjelm C, Warstedt K, Larsson J, Fredriksson M, Bottcher MF, Falth-Magnusson K, et al. Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy. Acta Paediatr. 2009;98(9):1461–7.

    Article  PubMed  Google Scholar 

  21. Kull I, Bergstrom A, Lilja G, Pershagen G, Wickman M. Fish consumption during the first year of life and development of allergic diseases during childhood. Allergy. 2006;61(8):1009–15.

    Article  CAS  PubMed  Google Scholar 

  22. Milner JD, Stein DM, McCarter R, Moon RY. Early infant multivitamin supplementation is associated with increased risk for food allergy and asthma. Pediatrics. 2004;114(1):27–32.

    Article  PubMed  Google Scholar 

  23. Kulig M, Luck W, Lau S, Niggemann B, Bergmann R, Klettke U, et al. Effect of pre- and postnatal tobacco smoke exposure on specific sensitization to food and inhalant allergens during the first 3 years of life. Multicenter Allergy Study Group, Germany. Allergy. 1999;54(3):220–8.

    Article  CAS  PubMed  Google Scholar 

  24. Lannero E, Wickman M, van Hage M, Bergstrom A, Pershagen G, Nordvall L. Exposure to environmental tobacco smoke and sensitisation in children. Thorax. 2008;63(2):172–6.

    Article  CAS  PubMed  Google Scholar 

  25. Bowatte G, Lodge C, Lowe AJ, Erbas B, Perret J, Abramson MJ, et al. The influence of childhood traffic-related air pollution exposure on asthma, allergy and sensitization: a systematic review and a meta-analysis of birth cohort studies. Allergy. 2015;70(3):245–56.

    Article  CAS  PubMed  Google Scholar 

  26. Ji H, Khurana Hershey GK. Genetic and epigenetic influence on the response to environmental particulate matter. J Allergy Clin Immunol. 2012;129(1):33–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hikino S, Nakayama H, Yamamoto J, Kinukawa N, Sakamoto M, Hara T. Food allergy and atopic dermatitis in low birthweight infants during early childhood. Acta Paediatr. 2001;90(8):850–5.

    Article  CAS  PubMed  Google Scholar 

  28. Chandran U, Demissie K, Echeverria SE, Long JB, Mizan S, Mino J. Food allergy among low birthweight children in a national survey. Matern Child Health J. 2013;17(1):165–71.

    Article  PubMed  Google Scholar 

  29. Eggesbo M, Botten G, Stigum H, Nafstad P, Magnus P. Is delivery by cesarean section a risk factor for food allergy? J Allergy Clin Immunol. 2003;112(2):420–6.

    Article  PubMed  Google Scholar 

  30. Lewis MC, Inman CF, Patel D, Schmidt B, Mulder I, Miller B, et al. Direct experimental evidence that early-life farm environment influences regulation of immune responses. Pediatr Allergy Immunol. 2012;23(3):265–9.

    Article  PubMed  Google Scholar 

  31. Negele K, Heinrich J, Borte M, von Berg A, Schaaf B, Lehmann I, et al. Mode of delivery and development of atopic disease during the first 2 years of life. Pediatr Allergy Immunol. 2004;15(1):48–54.

    Article  PubMed  Google Scholar 

  32. Noverr MC, Huffnagle GB. The ‘microflora hypothesis’ of allergic diseases. Clin Exp Allergy. 2005;35(12):1511–20.

    Article  CAS  PubMed  Google Scholar 

  33. Sanchez-Valverde F, Gil F, Martinez D, Fernandez B, Aznal E, Oscoz M, et al. The impact of caesarean delivery and type of feeding on cow’s milk allergy in infants and subsequent development of allergic march in childhood. Allergy. 2009;64(6):884–9.

    Article  CAS  PubMed  Google Scholar 

  34. Brand S, Teich R, Dicke T, Harb H, Yildirim AO, Tost J, et al. Epigenetic regulation in murine offspring as a novel mechanism for transmaternal asthma protection induced by microbes. J Allergy Clin Immunol. 2011;128(3):618-25 e1-7.

  35. Kumar R, Tsai HJ, Hong X, Liu X, Wang G, Pearson C, et al. Race, ancestry, and development of food-allergen sensitization in early childhood. Pediatrics. 2011;128(4):e821–9.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Liu AH, Jaramillo R, Sicherer SH, Wood RA, Bock SA, Burks AW, et al. National prevalence and risk factors for food allergy and relationship to asthma: results from the National Health and Nutrition Examination Survey 2005-2006. J Allergy Clin Immunol. 2010;126(4):798–806 e13.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Sicherer SH, Munoz-Furlong A, Sampson HA. Prevalence of seafood allergy in the United States determined by a random telephone survey. J Allergy Clin Immunol. 2004;114(1):159–65.

    Article  PubMed  Google Scholar 

  38. Hong X, Wang X. Early life precursors, epigenetics, and the development of food allergy. Semin Immunopathol. 2012;34(5):655–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Liu X, Zhang S, Tsai HJ, Hong X, Wang B, Fang Y, et al. Genetic and environmental contributions to allergen sensitization in a Chinese twin study. Clin Exp Allergy. 2009;39(7):991–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. •• Hong X, Hao K, Ladd-Acosta C, Hansen KD, Tsai HJ, Liu X, et al. Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children. Nat Commun. 2015;6:6304. This GWAS study of 2759 food allergic participants (1315 children, 1444 parents), found two peanut allergy specific loci in the HLA-DR and -DQ gene regions. The SNPs in these regions are associated with differential DNA methylation of HLA-DQB1 and HLA-DRB1 and suggests that this gene region is a risk factor for peanut allergy.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Gough SC, Simmonds MJ. The HLA Region and Autoimmune Disease: Associations and Mechanisms of Action. Curr Genomics. 2007;8(7):453–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Howell WM, Turner SJ, Hourihane JO, Dean TP, Warner JO. HLA class II DRB1, DQB1 and DPB1 genotypic associations with peanut allergy: evidence from a family-based and case-control study. Clin Exp Allergy. 1998;28(2):156–62.

    Article  CAS  PubMed  Google Scholar 

  43. Kontakioti E, Domvri K, Papakosta D, Daniilidis M. HLA and asthma phenotypes/endotypes: a review. Hum Immunol. 2014;75(8):930–9.

    Article  CAS  PubMed  Google Scholar 

  44. Robinson JH, Delvig AA. Diversity in MHC class II antigen presentation. Immunology. 2002;105(3):252–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. • Martino D, Joo JE, Sexton-Oates A, Dang T, Allen K, Saffery R, et al. Epigenome-wide association study reveals longitudinally stable DNA methylation differences in CD4+ T cells from children with IgE-mediated food allergy. Epigenetics. 2014;9(7):998–1006. Using a birth cohort, Martino et al examined the methylation profile of 12 food allergic one year olds and 12 age matched controls at birth and at 12 months. They found 179 differentially methylated regions at 12 months, but 136 regions at birth compared to the control group.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Kondo N, Kobayashi Y, Shinoda S, Kasahara K, Kameyama T, Iwasa S, et al. Cord blood lymphocyte responses to food antigens for the prediction of allergic disorders. Arch Dis Child. 1992;67(8):1003–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Prescott SL, Macaubas C, Smallacombe T, Holt BJ, Sly PD, Loh R, et al. Reciprocal age-related patterns of allergen-specific T-cell immunity in normal vs. atopic infants. Clin Exp Allergy. 1998;28 Suppl 5:39-44; discussion 50-1.

  48. Tang ML, Kemp AS, Thorburn J, Hill DJ. Reduced interferon-gamma secretion in neonates and subsequent atopy. Lancet. 1994;344(8928):983–5.

    Article  CAS  PubMed  Google Scholar 

  49. Martino DJ, Bosco A, McKenna KL, Hollams E, Mok D, Holt PG, et al. T-cell activation genes differentially expressed at birth in CD4+ T-cells from children who develop IgE food allergy. Allergy. 2012;67(2):191–200.

    Article  CAS  PubMed  Google Scholar 

  50. •• Hong X, Ladd-Acosta C, Hao K, Sherwood B, Ji H, Keet CA, et al. Epigenome-wide association study links site-specific DNA methylation changes with cow’s milk allergy. J Allergy Clin Immunol. 2016. Hong et al. took 106 children with cow’s milk allergy (CMA) and 76 non-atopic controls and measured DNA methylation levels at 485,512 genomic loci. For those differentially methylated regions in relation to CMA, two replication cohorts ( n  = 25 and 140) were used to validate findings. Results found eight validated regions with association to CMA, including three novel regions.

  51. • Swamy RS, Reshamwala N, Hunter T, Vissamsetti S, Santos CB, Baroody FM, et al. Epigenetic modifications and improved regulatory T-cell function in subjects undergoing dual sublingual immunotherapy. J Allergy Clin Immunol. 2012;130(1):215–24 e7. In a study examing environmental allergy sublingual immunotherapy (SLIT) to timothy grass and dust mite, Swamy et al. found that active SLIT reduced DNAm of CpG sites within the FOXP3 locus compared to receiving control treatment.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. •• Syed A, Garcia MA, Lyu SC, Bucayu R, Kohli A, Ishida S, et al. Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3). J Allergy Clin Immunol. 2014;133(2):500–10. This study compared allergic patients undergoing OIT (n = 24) or continuing to abstain from peanut (n = 20). T-cell function along with demethylation of FOXP3 CpG sites were significantly different between the two groups. However, this change was not permanent as some patients who had withdrawn from therapy regained sensitivity and had increased methylation of FOXP3 CpG sites after three months.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. •• Berni Canani R, Paparo L, Nocerino R, Cosenza L, Pezzella V, Di Costanzo M, et al. Differences in DNA methylation profile of Th1 and Th2 cytokine genes are associated with tolerance acquisition in children with IgE-mediated cow’s milk allergy. Clin Epigenetics. 2015;7:38. Canani et al took 10 CMA children, 20 children who had outgrown their CMA, and 10 control children to compare DNAm levels in CpG regions along with their respective cytokine levels of IL-4, IL-5, IL-10, and INF-γ. The combination of DNAm levels was distinct between active CMA and healthy controls. This provides evidence that DNAm plays a role in Th1/Th2 imbalance seen in food allergy.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Tang ML, Ponsonby AL, Orsini F, Tey D, Robinson M, Su EL, et al. Administration of a probiotic with peanut oral immunotherapy: A randomized trial. J Allergy Clin Immunol. 2015;135(3):737–44 e8.

    Article  CAS  PubMed  Google Scholar 

  55. Viljanen M, Kuitunen M, Haahtela T, Juntunen-Backman K, Korpela R, Savilahti E. Probiotic effects on faecal inflammatory markers and on faecal IgA in food allergic atopic eczema/dermatitis syndrome infants. Pediatr Allergy Immunol. 2005;16(1):65–71.

    Article  PubMed  Google Scholar 

  56. Pessi T, Sutas Y, Hurme M, Isolauri E. Interleukin-10 generation in atopic children following oral Lactobacillus rhamnosus GG. Clin Exp Allergy. 2000;30(12):1804–8.

    Article  CAS  PubMed  Google Scholar 

  57. Berni Canani R, Sangwan N, Stefka AT, Nocerino R, Paparo L, Aitoro R, et al. Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants. ISME J. 2016;10(3):742–50.

    Article  PubMed  Google Scholar 

  58. •• Martino D, Dang T, Sexton-Oates A, Prescott S, Tang ML, Dharmage S, et al. Blood DNA methylation biomarkers predict clinical reactivity in food-sensitized infants. J Allergy Clin Immunol. 2015;135(5):1319-28 e1-12. Martino et al. created a panel consisting of DNAm levels in 96 CpG sites which could predict food challenge outcomes. Using a replication cohort, this panel was able to predict the outcome at a rate of 79.2%. This panel was able to outperform both skin prick test and allergen specific IgE test in this regard.

  59. Treangen TJ, Salzberg SL. Repetitive DNA and next-generation sequencing: computational challenges and solutions. Nat Rev Genet. 2012;13(1):36–46.

    CAS  Google Scholar 

  60. Leek JT, Scharpf RB, Bravo HC, Simcha D, Langmead B, Johnson WE, et al. Tackling the widespread and critical impact of batch effects in high-throughput data. Nat Rev Genet. 2010;11(10):733–9.

    Article  CAS  PubMed  Google Scholar 

  61. Quail MA, Smith M, Coupland P, Otto TD, Harris SR, Connor TR, et al. A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers. BMC Genomics. 2012;13:341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Boyes J, Bird A. DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein. Cell. 1991;64(6):1123–34.

    Article  CAS  PubMed  Google Scholar 

  63. Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature. 1998;393(6683):386–9.

    Article  CAS  PubMed  Google Scholar 

  64. Murr R. Interplay between different epigenetic modifications and mechanisms. Adv Genet. 2010;70:101–41.

    CAS  PubMed  Google Scholar 

  65. Weissmann F, Lyko F. Cooperative interactions between epigenetic modifications and their function in the regulation of chromosome architecture. Bioessays. 2003;25(8):792–7.

    Article  CAS  PubMed  Google Scholar 

  66. Qu K, Zaba LC, Giresi PG, Li R, Longmire M, Kim YH, et al. Individuality and variation of personal regulomes in primary human T cells. Cell Syst. 2015;1(1):51–61.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, et al. Integrative analysis of 111 reference human epigenomes. Nature. 2015;518(7539):317–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, et al. Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet. 2008;40(7):897–903.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Dey A, Chitsaz F, Abbasi A, Misteli T, Ozato K. The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis. Proc Natl Acad Sci U S A. 2003;100(15):8758–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Zeng L, Zhang Q, Li S, Plotnikov AN, Walsh MJ, Zhou MM. Mechanism and regulation of acetylated histone binding by the tandem PHD finger of DPF3b. Nature. 2010;466(7303):258–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Tessarz P, Kouzarides T. Histone core modifications regulating nucleosome structure and dynamics. Nat Rev Mol Cell Biol. 2014;15(11):703–8.

    Article  CAS  PubMed  Google Scholar 

  72. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, et al. High-resolution profiling of histone methylations in the human genome. Cell. 2007;129(4):823–37.

    Article  CAS  PubMed  Google Scholar 

  73. • Wei G, Wei L, Zhu J, Zang C, Hu-Li J, Yao Z, et al. Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. Immunity. 2009;30(1):155–67. Wei et al. was able to show specific histone modifications and their relation to CD4+ T cells, providing support that epigenetic regulation plays a role in immune balance.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Margueron R, Reinberg D. Chromatin structure and the inheritance of epigenetic information. Nat Rev Genet. 2010;11(4):285–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat Methods. 2013;10(12):1213–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Buenrostro JD, Wu B, Chang HY, Greenleaf WJ. ATAC-seq: A Method for Assaying Chromatin Accessibility Genome-Wide. Curr Protoc Mol Biol. 2015;109:21 9 1-9.

  77. Tsompana M, Buck MJ. Chromatin accessibility: a window into the genome. Epigenetics Chromatin. 2014;7(1):33.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Niwa R, Slack FJ. The evolution of animal microRNA function. Curr Opin Genet Dev. 2007;17(2):145–50.

    Article  CAS  PubMed  Google Scholar 

  79. Christodoulou F, Raible F, Tomer R, Simakov O, Trachana K, Klaus S, et al. Ancient animal microRNAs and the evolution of tissue identity. Nature. 2010;463(7284):1084–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009;11(3):228–34.

    Article  CAS  PubMed  Google Scholar 

  81. •• Lu TX, Rothenberg ME. Diagnostic, functional, and therapeutic roles of microRNA in allergic diseases. J Allergy Clin Immunol. 2013;132(1):3-13; quiz 4. Lu et al detailed the relation between regulatory mechanisms of allergic inflammation and specific miRNA. MiRNA has been associated with TH1/TH2 balance, T-cell activation, and other pathways critical to atopic disease.

  82. Lu TX, Munitz A, Rothenberg ME. MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression. J Immunol. 2009;182(8):4994–5002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Sonkoly E, Wei T, Janson PC, Saaf A, Lundeberg L, Tengvall-Linder M, et al. MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? PLoS One. 2007;2(7):e610.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Collison A, Mattes J, Plank M, Foster PS. Inhibition of house dust mite-induced allergic airways disease by antagonism of microRNA-145 is comparable to glucocorticoid treatment. J Allergy Clin Immunol. 2011;128(1):160–7 e4.

    Article  CAS  PubMed  Google Scholar 

  85. Lu TX, Lim EJ, Besse JA, Itskovich S, Plassard AJ, Fulkerson PC, et al. MiR-223 deficiency increases eosinophil progenitor proliferation. J Immunol. 2013;190(4):1576–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. •• Lu TX, Sherrill JD, Wen T, Plassard AJ, Besse JA, Abonia JP, et al. MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers. J Allergy Clin Immunol. 2012;129(4):1064-75 e9. Lu et al provided evidence that there are distinct changes in miRNA expression associated with eosinophilic esophagitis, providing one of the first studys showing the value of miRNA as a biomarker in atopic disease.

  87. Shaoqing Y, Ruxin Z, Guojun L, Zhiqiang Y, Hua H, Shudong Y, et al. Microarray analysis of differentially expressed microRNAs in allergic rhinitis. Am J Rhinol Allergy. 2011;25(6):e242–6.

    Article  PubMed  Google Scholar 

  88. Brouzes E, Medkova M, Savenelli N, Marran D, Twardowski M, Hutchison JB, et al. Droplet microfluidic technology for single-cell high-throughput screening. Proc Natl Acad Sci U S A. 2009;106(34):14195–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by the Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine (Bunning, DeKruyff, Nadeau) and by the National Institutes of Health Grants: PO1 AI-054456 (DeKruyff). Thank you to Vanitha Sampath and Ivan T. Lee for their help on the finalization of this review.

Author information

Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University, Stanford, CA, USA

    Bryan J. Bunning, Rosemarie H. DeKruyff & Kari C. Nadeau

  2. Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, USA

    Bryan J. Bunning, Rosemarie H. DeKruyff & Kari C. Nadeau

  3. Sean N. Parker Center for Allergy and Asthma Research, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University, Stanford University School of Medicine, 269 Campus Drive, CCSR 3215, MC 5366, Stanford, CA, 94305-5101, USA

    Kari C. Nadeau

Authors
  1. Bryan J. Bunning
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rosemarie H. DeKruyff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kari C. Nadeau
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kari C. Nadeau.

Ethics declarations

Conflict of Interest

The authors declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Immunotherapy and Immunomodulators

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bunning, B.J., DeKruyff, R.H. & Nadeau, K.C. Epigenetic Changes During Food-Specific Immunotherapy. Curr Allergy Asthma Rep 16, 87 (2016). https://doi.org/10.1007/s11882-016-0665-y

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11882-016-0665-y

Keywords

Search

Navigation