Top

Current Gastroenterology Reports

Published in:

11-11-2023 | Eosinophilic Esophagitis

Barrier Dysfunction in Eosinophilic Esophagitis

Authors: Emily C. McGowan, Roopesh Singh, David A. Katzka

Published in: Current Gastroenterology Reports | Issue 12/2023

Abstract

Purpose of Review

Compelling evidence over the past decade supports the central role of epithelial barrier dysfunction in the pathophysiology of eosinophilic esophagitis (EoE). The purpose of this review is to summarize the genetic, environmental, and immunologic factors driving epithelial barrier dysfunction, and how this impaired barrier can further promote the inflammatory response in EoE.

Recent Findings

Common environmental exposures, such as detergents, may have a direct impact on the esophageal epithelial barrier. In addition, the effects of IL-13 on barrier dysfunction may be reduced by 17β-estradiol, Vitamin D, and the short chain fatty acids butyrate and propionate, suggesting novel therapeutic targets.

Summary

There are many genetic, environmental, and immunologic factors that contribute to epithelial barrier dysfunction in EoE. This leads to further skewing of the immune response to a “Th2” phenotype, alterations in the esophageal microbiome, and penetration of relevant antigens into the esophageal mucosa, which are central to the pathophysiology of EoE.

Dobbins JW, Sheahan DG, Behar J. Eosinophilic gastroenteritis with esophageal involvement. Gastroenterology. 1977;72(6):1312–6.CrossRefPubMed

Kerlin P, Jones D, Remedios M, Campbell C. Prevalence of eosinophilic esophagitis in adults with food bolus obstruction of the esophagus. J Clin Gastroenterol. 2007;41(4):356–61. https://doi.org/10.1097/01.mcg.0000225590.08825.77.CrossRefPubMed

Kirchner GI, Zuber-Jerger I, Endlicher E, Gelbmann C, Ott C, Ruemmele P, et al. Causes of bolus impaction in the esophagus. Surg Endosc. 2011;25(10):3170–4. https://doi.org/10.1007/s00464-011-1681-6.CrossRefPubMed

Diniz LO, Towbin AJ. Causes of esophageal food bolus impaction in the pediatric population. Dig Dis Sci. 2012;57(3):690–3. https://doi.org/10.1007/s10620-011-1911-8.CrossRefPubMed

Dellon ES, Liacouras CA, Molina-Infante J, Furuta GT, Spergel JM, Zevit N, et al. Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference. Gastroenterology. 2018;155(4):1022-33.e10. https://doi.org/10.1053/j.gastro.2018.07.009.CrossRefPubMed

Kelly KJ, Lazenby AJ, Rowe PC, Yardley JH, Perman JA, Sampson HA. Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula. Gastroenterology. 1995;109(5):1503–12. https://doi.org/10.1016/0016-5085(95)90637-1.CrossRefPubMed

Peterson KA, Byrne KR, Vinson LA, Ying J, Boynton KK, Fang JC, et al. Elemental diet induces histologic response in adult eosinophilic esophagitis. Am J Gastroenterol. 2013;108(5):759–66. https://doi.org/10.1038/ajg.2012.468.CrossRefPubMed

Kagalwalla AF, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM, et al. Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2006;4(9):1097–102. https://doi.org/10.1016/j.cgh.2006.05.026.CrossRefPubMed

Molina-Infante J, Arias Á, Alcedo J, Garcia-Romero R, Casabona-Frances S, Prieto-Garcia A, et al. Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: The 2–4-6 study. J Allergy Clin Immunol. 2018;141(4):1365–72. https://doi.org/10.1016/j.jaci.2017.08.038.CrossRefPubMed

10.

Cookson WO, Ubhi B, Lawrence R, Abecasis GR, Walley AJ, Cox HE, et al. Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci. Nat Genet. 2001;27(4):372–3. https://doi.org/10.1038/86867.CrossRefPubMed

11.

Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet. 2006;38(4):441–6. https://doi.org/10.1038/ng1767.CrossRefPubMed

12.

Irvine AD. Fleshing out filaggrin phenotypes. J Invest Dermatol. 2007;127(3):504–7. https://doi.org/10.1038/sj.jid.5700695.CrossRefPubMed

13.

Blanchard C, Stucke EM, Burwinkel K, Caldwell JM, Collins MH, Ahrens A, et al. Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis. J Immunol. 2010;184(7):4033–41. https://doi.org/10.4049/jimmunol.0903069.CrossRefPubMed

14.

Katzka DA, Tadi R, Smyrk TC, Katarya E, Sharma A, Geno DM, et al. Effects of topical steroids on tight junction proteins and spongiosis in esophageal epithelia of patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2014;12(11):1824-9.e1. https://doi.org/10.1016/j.cgh.2014.02.039.CrossRefPubMed

15.

Katzka DA, Ravi K, Geno DM, Smyrk TC, Iyer PG, Alexander JA, et al. Endoscopic mucosal impedance measurements correlate with eosinophilia and dilation of intercellular spaces in patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2015;13(7):1242-8.e1. https://doi.org/10.1016/j.cgh.2014.12.032.CrossRefPubMed

16.

Vaezi MF, Choksi Y. Mucosal impedance: a new way to diagnose reflux disease and how it could change your practice. Am J Gastroenterol. 2017;112(1):4–7. https://doi.org/10.1038/ajg.2016.513.CrossRefPubMed

17.

Patel DA, Higginbotham T, Slaughter JC, Aslam M, Yuksel E, Katzka D, et al. Development and validation of a mucosal impedance contour analysis system to distinguish esophageal disorders. Gastroenterology. 2019;156(6):1617-26.e1. https://doi.org/10.1053/j.gastro.2019.01.253.CrossRefPubMed

18.

Sifrim D, Roman S, Savarino E, Bor S, Bredenoord AJ, Castell D, et al. Normal values and regional differences in oesophageal impedance-pH metrics: a consensus analysis of impedance-pH studies from around the world. Gut. 2020. https://doi.org/10.1136/gutjnl-2020-322627.CrossRefPubMed

19.

Wallace MB, Fockens P. Probe-based confocal laser endomicroscopy. Gastroenterology. 2009;136(5):1509–13. https://doi.org/10.1053/j.gastro.2009.03.034.CrossRefPubMed

20.

Chu CL, Zhen YB, Lv GP, Li CQ, Li Z, Qi QQ, et al. Microalterations of esophagus in patients with non-erosive reflux disease: in-vivo diagnosis by confocal laser endomicroscopy and its relationship with gastroesophageal reflux. Am J Gastroenterol. 2012;107(6):864–74. https://doi.org/10.1038/ajg.2012.44.CrossRefPubMed

21.

Kiesslich R, Gossner L, Goetz M, Dahlmann A, Vieth M, Stolte M, et al. In vivo histology of Barrett’s esophagus and associated neoplasia by confocal laser endomicroscopy. Clin Gastroenterol Hepatol. 2006;4(8):979–87. https://doi.org/10.1016/j.cgh.2006.05.010.CrossRefPubMed

22.

Fritscher-Ravens A, Schuppan D, Ellrichmann M, Schoch S, Röcken C, Brasch J, et al. Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology. 2014;147(5):1012-20.e4. https://doi.org/10.1053/j.gastro.2014.07.046.CrossRefPubMed

23.

Blevins CH, Sharma AN, Johnson ML, Geno D, Gupta M, Bharucha AE, et al. Influence of reflux and central obesity on intercellular space diameter of esophageal squamous epithelium. U Eur Gastroenterol J. 2016;4(2):177–83. https://doi.org/10.1177/2050640615598426.CrossRef

24.

van Rhijn BD, Verheij J, van den Bergh Weerman MA, Verseijden C, van den Wijngaard RM, de Jonge WJ, et al. Histological response to fluticasone propionate in patients with eosinophilic esophagitis is associated with improved functional esophageal mucosal integrity. Am J Gastroenterol. 2015;110(9):1289–97. https://doi.org/10.1038/ajg.2015.247.CrossRefPubMed

25.

Wu L, Oshima T, Li M, Tomita T, Fukui H, Watari J, et al. Filaggrin and tight junction proteins are crucial for IL-13-mediated esophageal barrier dysfunction. Am J Physiol Gastrointest Liver Physiol. 2018;315(3):G341–50. https://doi.org/10.1152/ajpgi.00404.2017.CrossRefPubMed

26.

Simon D, Page B, Vogel M, Bussmann C, Blanchard C, Straumann A, et al. Evidence of an abnormal epithelial barrier in active, untreated and corticosteroid-treated eosinophilic esophagitis. Allergy. 2018;73(1):239–47. https://doi.org/10.1111/all.13244.CrossRefPubMed

27.

Masterson JC, Biette KA, Hammer JA, Nguyen N, Capocelli KE, Saeedi BJ, et al. Epithelial HIF-1α/claudin-1 axis regulates barrier dysfunction in eosinophilic esophagitis. J Clin Invest. 2019;129(8):3224–35. https://doi.org/10.1172/jci126744.CrossRefPubMedPubMedCentral

28.

Sherrill JD, Kc K, Wu D, Djukic Z, Caldwell JM, Stucke EM, et al. Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis. Mucosal Immunol. 2014;7(3):718–29. https://doi.org/10.1038/mi.2013.90.CrossRefPubMed

29.

de Rooij WE, Diks MAP, Warners MJ, Ampting M, van Esch B, Bredenoord AJ. Gene expression and clinical outcomes after dietary treatment for eosinophilic esophagitis: a prospective study. Neurogastroenterol Motil. 2022;34(10):e14367. https://doi.org/10.1111/nmo.14367.CrossRefPubMedPubMedCentral

30.

van Rhijn BD, Weijenborg PW, Verheij J, van den Bergh Weerman MA, Verseijden C, van den Wijngaard RM, et al. Proton pump inhibitors partially restore mucosal integrity in patients with proton pump inhibitor-responsive esophageal eosinophilia but not eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2014;12(11):1815-23.e2. https://doi.org/10.1016/j.cgh.2014.02.037.CrossRefPubMed

31.

Lowry MA, Vaezi MF, Correa H, Higginbotham T, Slaughter JC, Acra S. Mucosal impedance measurements differentiate pediatric patients with active versus inactive eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2018;67(2):198–203. https://doi.org/10.1097/mpg.0000000000001943.CrossRefPubMedPubMedCentral

32.

Alexander JA, Ravi K, Geno DM, Tholen CJ, Higginbotham TC, Wildhorn S, et al. Comparison of mucosal impedance measurements throughout the esophagus and mucosal eosinophil counts in endoscopic biopsy specimens in eosinophilic esophagitis. Gastrointest Endosc. 2019;89(4):693-700.e1. https://doi.org/10.1016/j.gie.2018.08.031.CrossRefPubMed

33.

Rothenberg ME, Spergel JM, Sherrill JD, Annaiah K, Martin LJ, Cianferoni A, et al. Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat Genet. 2010;42(4):289–91. https://doi.org/10.1038/ng.547.CrossRefPubMedPubMedCentral

34.

Kottyan LC, Davis BP, Sherrill JD, Liu K, Rochman M, Kaufman K, et al. Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease. Nat Genet. 2014;46(8):895–900. https://doi.org/10.1038/ng.3033.CrossRefPubMedPubMedCentral

35.

Blanchard C, Wang N, Stringer KF, Mishra A, Fulkerson PC, Abonia JP, et al. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest. 2006;116(2):536–47. https://doi.org/10.1172/jci26679.CrossRefPubMedPubMedCentral

36.

Kottyan LC, Rothenberg ME. Genetics of eosinophilic esophagitis. Mucosal Immunol. 2017;10(3):580–8. https://doi.org/10.1038/mi.2017.4.CrossRefPubMedPubMedCentral

37.

Kottyan LC, Parameswaran S, Weirauch MT, Rothenberg ME, Martin LJ. The genetic etiology of eosinophilic esophagitis. J Allergy Clin Immunol. 2020;145(1):9–15. https://doi.org/10.1016/j.jaci.2019.11.013.CrossRefPubMedPubMedCentral

38.•

Kalb B, Marenholz I, Jeanrenaud A, Meixner L, Arnau-Soler A, Rosillo-Salazar OD, et al. Filaggrin loss-of-function mutations are associated with persistence of egg and milk allergy. J Allergy Clin Immunol. 2022;150(5):1125–34. https://doi.org/10.1016/j.jaci.2022.05.018. This study demonstrates that FLG loss-of-function mutations are a risk factor for food allergy independent of eczema.CrossRefPubMed

39.

Brown SJ, Asai Y, Cordell HJ, Campbell LE, Zhao Y, Liao H, et al. Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. J Allergy Clin Immunol. 2011;127(3):661–7. https://doi.org/10.1016/j.jaci.2011.01.031.CrossRefPubMedPubMedCentral

40.

Rice NE, Patel BD, Lang IA, Kumari M, Frayling TM, Murray A, et al. Filaggrin gene mutations are associated with asthma and eczema in later life. J Allergy Clin Immunol. 2008;122(4):834–6. https://doi.org/10.1016/j.jaci.2008.07.027.CrossRefPubMedPubMedCentral

41.

Matoso A, Mukkada VA, Lu S, Monahan R, Cleveland K, Noble L, et al. Expression microarray analysis identifies novel epithelial-derived protein markers in eosinophilic esophagitis. Mod Pathol. 2013;26(5):665–76. https://doi.org/10.1038/modpathol.2013.41.CrossRefPubMed

42.

Blanchard C, Mingler MK, Vicario M, Abonia JP, Wu YY, Lu TX, et al. IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids. J Allergy Clin Immunol. 2007;120(6):1292–300. https://doi.org/10.1016/j.jaci.2007.10.024.CrossRefPubMed

43.

Noti M, Wojno ED, Kim BS, Siracusa MC, Giacomin PR, Nair MG, et al. Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis. Nat Med. 2013;19(8):1005–13. https://doi.org/10.1038/nm.3281.CrossRefPubMedPubMedCentral

44.

Sherrill JD, Gao PS, Stucke EM, Blanchard C, Collins MH, Putnam PE, et al. Variants of thymic stromal lymphopoietin and its receptor associate with eosinophilic esophagitis. J Allergy Clin Immunol. 2010;126(1):160-5.e3. https://doi.org/10.1016/j.jaci.2010.04.037.CrossRefPubMedPubMedCentral

45.

Hammad H, Lambrecht BN. Barrier epithelial cells and the control of Type 2 immunity. Immunity. 2015;43(1):29–40. https://doi.org/10.1016/j.immuni.2015.07.007.CrossRefPubMed

46.

Chandramouleeswaran PM, Shen D, Lee AJ, Benitez A, Dods K, Gambanga F, et al. Preferential secretion of Thymic stromal Lymphopoietin (TSLP) by terminally differentiated esophageal epithelial cells: relevance to eosinophilic esophagitis (EoE). PLoS ONE. 2016;11(3):e0150968. https://doi.org/10.1371/journal.pone.0150968.CrossRefPubMedPubMedCentral

47.

Ramasamy A, Kuokkanen M, Vedantam S, Gajdos ZK, Couto Alves A, Lyon HN, et al. Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA. PLoS One. 2012;7(9):e44008. https://doi.org/10.1371/journal.pone.0044008.CrossRefPubMedPubMedCentral

48.

Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S, et al. A large-scale, consortium-based genomewide association study of asthma. N Engl J Med. 2010;363(13):1211–21. https://doi.org/10.1056/NEJMoa0906312.CrossRefPubMedPubMedCentral

49.

Martin LJ, He H, Collins MH, Abonia JP, Biagini Myers JM, Eby M, et al. Eosinophilic esophagitis (EoE) genetic susceptibility is mediated by synergistic interactions between EoE-specific and general atopic disease loci. J Allergy Clin Immunol. 2018;141(5):1690–8. https://doi.org/10.1016/j.jaci.2017.09.046.CrossRefPubMed

50.

Judd LM, Heine RG, Menheniott TR, Buzzelli J, O’Brien-Simpson N, Pavlic D, et al. Elevated IL-33 expression is associated with pediatric eosinophilic esophagitis, and exogenous IL-33 promotes eosinophilic esophagitis development in mice. Am J Physiol Gastrointest Liver Physiol. 2016;310(1):G13-25. https://doi.org/10.1152/ajpgi.00290.2015.CrossRefPubMed

51.

Travers J, Rochman M, Caldwell JM, Besse JA, Miracle CE, Rothenberg ME. IL-33 is induced in undifferentiated, non-dividing esophageal epithelial cells in eosinophilic esophagitis. Sci Rep. 2017;7(1):17563. https://doi.org/10.1038/s41598-017-17541-5.CrossRefPubMedPubMedCentral

52.

Marwaha AK, Laxer R, Liang M, Muise AM, Eiwegger T. A chromosomal duplication encompassing Interleukin-33 causes a novel hyper IgE phenotype characterized by eosinophilic esophagitis and generalized autoimmunity. Gastroenterology. 2022;163(2):510-3.e3. https://doi.org/10.1053/j.gastro.2022.04.026.CrossRefPubMed

53.

Sleiman PM, Wang ML, Cianferoni A, Aceves S, Gonsalves N, Nadeau K, et al. GWAS identifies four novel eosinophilic esophagitis loci. Nat Commun. 2014;5:5593. https://doi.org/10.1038/ncomms6593.CrossRefPubMed

54.

Davis BP, Stucke EM, Khorki ME, Litosh VA, Rymer JK, Rochman M, et al. Eosinophilic esophagitis-linked calpain 14 is an IL-13-induced protease that mediates esophageal epithelial barrier impairment. JCI Insight. 2016;1(4):e86355. https://doi.org/10.1172/jci.insight.86355.CrossRefPubMedPubMedCentral

55.

Litosh VA, Rochman M, Rymer JK, Porollo A, Kottyan LC, Rothenberg ME. Calpain-14 and its association with eosinophilic esophagitis. J Allergy Clin Immunol. 2017;139(6):1762-71.e7. https://doi.org/10.1016/j.jaci.2016.09.027.CrossRefPubMedPubMedCentral

56.

Alexander ES, Martin LJ, Collins MH, Kottyan LC, Sucharew H, He H, et al. Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis. J Allergy Clin Immunol. 2014;134(5):1084-92.e1. https://doi.org/10.1016/j.jaci.2014.07.021.CrossRefPubMedPubMedCentral

57.

Jensen ET, Kuhl JT, Martin LJ, Rothenberg ME, Dellon ES. Prenatal, intrapartum, and postnatal factors are associated with pediatric eosinophilic esophagitis. J Allergy Clin Immunol. 2018;141(1):214–22. https://doi.org/10.1016/j.jaci.2017.05.018.CrossRefPubMed

58.•

Kurt G, Svane HML, Erichsen R, Heide-Jørgensen U, Sørensen HT, Dellon ES, et al. Prenatal, intrapartum, and neonatal factors increase the risk of eosinophilic esophagitis. Am J Gastroenterol. 2023. https://doi.org/10.14309/ajg.0000000000002303. This study identified environmental factors, including prenatal, intrapartum, and neonatal factors, associated with the development of EoE.CrossRefPubMed

59.

Dellon ES, Hirano I. Epidemiology and natural history of eosinophilic esophagitis. Gastroenterology. 2018;154(2):319-32.e3. https://doi.org/10.1053/j.gastro.2017.06.067.CrossRefPubMed

60.

Akdis CA. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat Rev Immunol. 2021;21(11):739–51. https://doi.org/10.1038/s41577-021-00538-7.CrossRefPubMed

61.

Singer MM, Tjeerdema RS. Fate and effects of the surfactant sodium dodecyl sulfate. Rev Environ Contam Toxicol. 1993;133:95–149. https://doi.org/10.1007/978-1-4613-9529-4_3.CrossRefPubMed

62.

Xian M, Wawrzyniak P, Rückert B, Duan S, Meng Y, Sokolowska M, et al. Anionic surfactants and commercial detergents decrease tight junction barrier integrity in human keratinocytes. J Allergy Clin Immunol. 2016;138(3):890-3.e9. https://doi.org/10.1016/j.jaci.2016.07.003.CrossRefPubMed

63.

Wang M, Tan G, Eljaszewicz A, Meng Y, Wawrzyniak P, Acharya S, et al. Laundry detergents and detergent residue after rinsing directly disrupt tight junction barrier integrity in human bronchial epithelial cells. J Allergy Clin Immunol. 2019;143(5):1892–903. https://doi.org/10.1016/j.jaci.2018.11.016.CrossRefPubMed

64.••

Doyle AD, Masuda MY, Pyon GC, Luo H, Putikova A, LeSuer WE, et al. Detergent exposure induces epithelial barrier dysfunction and eosinophilic inflammation in the esophagus. Allergy. 2023;78(1):192–201. https://doi.org/10.1111/all.15457. This study assessed the harmful effect of SDS exposure to eosophageal muscosa via in vitro as well as in vivo mouse models and found that detergents may be a key environmental trigger in EoE pathogenesis.CrossRefPubMed

65.

Hosoki K, Boldogh I, Sur S. Innate responses to pollen allergens. Curr Opin Allergy Clin Immunol. 2015;15(1):79–88. https://doi.org/10.1097/aci.0000000000000136.CrossRefPubMedPubMedCentral

66.

Vinhas R, Cortes L, Cardoso I, Mendes VM, Manadas B, Todo-Bom A, et al. Pollen proteases compromise the airway epithelial barrier through degradation of transmembrane adhesion proteins and lung bioactive peptides. Allergy. 2011;66(8):1088–98. https://doi.org/10.1111/j.1398-9995.2011.02598.x.CrossRefPubMed

67.

Wan H, Winton HL, Soeller C, Taylor GW, Gruenert DC, Thompson PJ, et al. The transmembrane protein occludin of epithelial tight junctions is a functional target for serine peptidases from faecal pellets of Dermatophagoides pteronyssinus. Clin Exp Allergy. 2001;31(2):279–94. https://doi.org/10.1046/j.1365-2222.2001.00970.x.CrossRefPubMed

68.

Ravi A, Marietta EV, Geno DM, Alexander JA, Murray JA, Katzka DA. Penetration of the esophageal epithelium by dust mite antigen in patients with eosinophilic esophagitis. Gastroenterology. 2019;157(1):255–6. https://doi.org/10.1053/j.gastro.2019.02.042.CrossRefPubMed

69.

Armentia A, Martín-Armentia S, Álvarez-Nogal R, Armentia BM, Gayoso MJ, Fernández-González D. Germination of pollen grains in the oesophagus of individuals with eosinophilic oesophagitis. Clin Exp Allergy. 2019;49(4):471–3. https://doi.org/10.1111/cea.13312.CrossRefPubMed

70.

Caraballo JC, Yshii C, Westphal W, Moninger T, Comellas AP. Ambient particulate matter affects occludin distribution and increases alveolar transepithelial electrical conductance. Respirology. 2011;16(2):340–9. https://doi.org/10.1111/j.1440-1843.2010.01910.x.CrossRefPubMedPubMedCentral

71.

Zhao R, Guo Z, Zhang R, Deng C, Xu J, Dong W, et al. Nasal epithelial barrier disruption by particulate matter ≤2.5 μm via tight junction protein degradation. J Appl Toxicol. 2018;38(5):678–87. https://doi.org/10.1002/jat.3573.CrossRefPubMed

72.

Bleck B, Grunig G, Chiu A, Liu M, Gordon T, Kazeros A, et al. MicroRNA-375 regulation of thymic stromal lymphopoietin by diesel exhaust particles and ambient particulate matter in human bronchial epithelial cells. J Immunol. 2013;190(7):3757–63. https://doi.org/10.4049/jimmunol.1201165.CrossRefPubMed

73.

Muir AB, Wang JX, Nakagawa H. Epithelial-stromal crosstalk and fibrosis in eosinophilic esophagitis. J Gastroenterol. 2019;54(1):10–8. https://doi.org/10.1007/s00535-018-1498-3.CrossRefPubMed

74.•

Gann PH, Deaton RJ, McMahon N, Collins MH, Dellon ES, Hirano I, et al. An anti-IL-13 antibody reverses epithelial-mesenchymal transition biomarkers in eosinophilic esophagitis: Phase 2 trial results. J Allergy Clin Immunol. 2020;146(2):367-76.e3. https://doi.org/10.1016/j.jaci.2020.03.045. This phase 2 clinical trial demonstrates that pharmacologic inhibition of IL-13 (anti‒IL-13 mAb) could be a potential therapy for fibrostenosis, the most serious eosinophilic esophagitis (EoE) complication.CrossRefPubMed

75.

Wheeler JC, Vanoni S, Zeng C, Waggoner L, Yang Y, Wu D, et al. 17β-Estradiol protects the esophageal epithelium from IL-13-induced barrier dysfunction and remodeling. J Allergy Clin Immunol. 2019;143(6):2131–46. https://doi.org/10.1016/j.jaci.2018.10.070.CrossRefPubMed

76.

Brusilovsky M, Rochman M, Shoda T, Kotliar M, Caldwell JM, Mack LE, et al. Vitamin D receptor and STAT6 interactome governs oesophageal epithelial barrier responses to IL-13 signalling. Gut. 2023;72(5):834–45. https://doi.org/10.1136/gutjnl-2022-327276.CrossRefPubMed

77.

Kleuskens MTA, Haasnoot ML, Herpers BM, Ampting M, Bredenoord AJ, Garssen J, et al. Butyrate and propionate restore interleukin 13-compromised esophageal epithelial barrier function. Allergy. 2022;77(5):1510–21. https://doi.org/10.1111/all.15069.CrossRefPubMed

78.

Aceves SS, Newbury RO, Dohil R, Bastian JF, Broide DH. Esophageal remodeling in pediatric eosinophilic esophagitis. J Allergy Clin Immunol. 2007;119(1):206–12. https://doi.org/10.1016/j.jaci.2006.10.016.CrossRefPubMed

79.

Aceves SS, Chen D, Newbury RO, Dohil R, Bastian JF, Broide DH. Mast cells infiltrate the esophageal smooth muscle in patients with eosinophilic esophagitis, express TGF-β1, and increase esophageal smooth muscle contraction. J Allergy Clin Immunol. 2010;126(6):1198-204.e4. https://doi.org/10.1016/j.jaci.2010.08.050.CrossRefPubMed

80.

Nguyen N, Fernando SD, Biette KA, Hammer JA, Capocelli KE, Kitzenberg DA, et al. TGF-β1 alters esophageal epithelial barrier function by attenuation of claudin-7 in eosinophilic esophagitis. Mucosal Immunol. 2018;11(2):415–26. https://doi.org/10.1038/mi.2017.72.CrossRefPubMed

81.

Laky K, Kinard JL, Li JM, Moore IN, Lack J, Fischer ER, et al. Epithelial-intrinsic defects in TGFβR signaling drive local allergic inflammation manifesting as eosinophilic esophagitis. Sci Immunol. 2023;8(79):eabp9940. https://doi.org/10.1126/sciimmunol.abp9940.CrossRefPubMedPubMedCentral

82.

Salamon P, Shoham NG, Puxeddu I, Paitan Y, Levi-Schaffer F, Mekori YA. Human mast cells release oncostatin M on contact with activated T cells: possible biologic relevance. J Allergy Clin Immunol. 2008;121(2):448-55.e5. https://doi.org/10.1016/j.jaci.2007.08.054.CrossRefPubMed

83.

Suda T, Chida K, Todate A, Ide K, Asada K, Nakamura Y, et al. Oncostatin M production by human dendritic cells in response to bacterial products. Cytokine. 2002;17(6):335–40. https://doi.org/10.1006/cyto.2002.1023.CrossRefPubMed

84.

Tamura S, Morikawa Y, Miyajima A, Senba E. Expression of oncostatin M in hematopoietic organs. Dev Dyn. 2002;225(3):327–31. https://doi.org/10.1002/dvdy.10156.CrossRefPubMed

85.

Pothoven KL, Norton JE, Hulse KE, Suh LA, Carter RG, Rocci E, et al. Oncostatin M promotes mucosal epithelial barrier dysfunction, and its expression is increased in patients with eosinophilic mucosal disease. J Allergy Clin Immunol. 2015;136(3):737-46.e4. https://doi.org/10.1016/j.jaci.2015.01.043.CrossRefPubMedPubMedCentral

86.

Kleuskens MTA, Bek MK, Al Halabi Y, Blokhuis BRJ, Diks MAP, Haasnoot ML, et al. Mast cells disrupt the function of the esophageal epithelial barrier. Mucosal Immunol. 2023. https://doi.org/10.1016/j.mucimm.2023.06.001.CrossRefPubMed

87.

Straumann A, Conus S, Grzonka P, Kita H, Kephart G, Bussmann C, et al. Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut. 2010;59(1):21–30. https://doi.org/10.1136/gut.2009.178558.CrossRefPubMed

88.

Assa’ad AH, Gupta SK, Collins MH, Thomson M, Heath AT, Smith DA, et al. An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis. Gastroenterology. 2011;141(5):1593–604. https://doi.org/10.1053/j.gastro.2011.07.044.CrossRefPubMed

89.

Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G 3rd, et al. Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2012;129(2):456–63. https://doi.org/10.1016/j.jaci.2011.11.044. (63.e1-3).CrossRefPubMed

90.

Benitez AJ, Hoffmann C, Muir AB, Dods KK, Spergel JM, Bushman FD, et al. Inflammation-associated microbiota in pediatric eosinophilic esophagitis. Microbiome. 2015;3:23. https://doi.org/10.1186/s40168-015-0085-6.CrossRefPubMedPubMedCentral

91.

Harris JK, Fang R, Wagner BD, Choe HN, Kelly CJ, Schroeder S, et al. Esophageal microbiome in eosinophilic esophagitis. PLoS ONE. 2015;10(5):e0128346. https://doi.org/10.1371/journal.pone.0128346.CrossRefPubMedPubMedCentral

92.

Norder Grusell E, Dahlén G, Ruth M, Bergquist H, Bove M. The cultivable bacterial flora of the esophagus in subjects with esophagitis. Scand J Gastroenterol. 2018;53(6):650–6. https://doi.org/10.1080/00365521.2018.1457712.CrossRefPubMed

93.••

Massimino L, Barchi A, Mandarino FV, Spanò S, Lamparelli LA, Vespa E, et al. A multi-omic analysis reveals the esophageal dysbiosis as the predominant trait of eosinophilic esophagitis. J Transl Med. 2023;21(1):46. https://doi.org/10.1186/s12967-023-03898-x. This study employed advanced bioinformatics and reanalyzed RNA-seq data of 18 different studies on EoE. This approach identified new EoE-specific molecular markers and also revealed microbiota dysbiosis as a predominant characteristic of EoE pathogenesis.CrossRefPubMedPubMedCentral

94.

Ravi A, Marietta EV, Alexander JA, Murray JA, Katzka DA (2023) H influenza LPS colocalization with Toll-like receptor 4 in eosinophilic esophagitis. JACI Global 2(4):100151

95.

Ravi A, Marietta EV, Alexander JA, Peterson K, Lavey C, Geno DM, et al. Mucosal penetration and clearance of gluten and milk antigens in eosinophilic oesophagitis. Aliment Pharmacol Ther. 2021;53(3):410–7. https://doi.org/10.1111/apt.16180.

96.••

Medernach JG, Li RC, Zhao XY, Yin B, Noonan EA, Etter EF, et al. Immunoglobulin G4 in eosinophilic esophagitis: Immune complex formation and correlation with disease activity. Allergy. 2023. https://doi.org/10.1111/all.15826. These data demonstrate that IgG4 and major cow's milk proteins are forming immune complexes in the esophageal tissue of patients with active EoE.

Title: Barrier Dysfunction in Eosinophilic Esophagitis
Authors: Emily C. McGowan
Roopesh Singh
David A. Katzka
Publication date: 11-11-2023
Publisher: Springer US
Keyword: Eosinophilic Esophagitis
Published in: Current Gastroenterology Reports / Issue 12/2023
Print ISSN: 1522-8037
Electronic ISSN: 1534-312X
DOI: https://doi.org/10.1007/s11894-023-00904-6

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

Please log in to get access to this content

Other articles of this Issue 12/2023

Revisiting Proton Pump Inhibitors as Chemoprophylaxis Against the Progression of Barrett’s Esophagus

ARFID at 10 years: A Review of Medical, Nutritional and Psychological Evaluation and Management

Small Bowel Imaging in Celiac Disease: Is there a role for Small Bowel Ultrasound?

Chronic Liver Disease in the Older Patient—Evaluation and Management

Esophageal Radiography Interpretation: a Primer for the Gastroenterologist

Hepatitis D Virus and HBsAg Dynamics in the era of new Antiviral Treatments

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage