Increased number of regulatory T cells in esophageal tissue of patients with eosinophilic esophagitis in comparison to gastro esophageal reflux disease and control groups
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Keywords
Eosinophilic esophagitis, EoE, GERD, Treg
Abstract
Background: Eosinophilic esophagitis (EoE) is a primarily polygenic allergic disorder. Although most patients have IgE sensitization, it seems that non-IgE mediated responses mainly contribute to the pathogenesis of EoE. Regulatory T cells (Tregs) may have an important role in allergies. There are limited data on the association of Tregs and EoE. In this study, we enumerated and compared T lymphocytes and Tregs in esophageal tissue of patients with EoE, gastroesophageal reflux disease (GERD) and normal controls.
Methods: Ten patients with EoE, ten patients with GERD and eight normal controls were included. Immunohistochemistry staining was used to enumerate T lymphocytes and Tregs. CD3+ cells were considered as T cells and FOXP3+, CD3+ cells were considered as Tregs. T cells and Tregs were counted in 10 high power fields (HPF) (×400) for each patient and the average of 10 HPFs was recorded.
Results: The mean ± SEM of Tregs in esophageal tissue of patients with EoE (10.90 ± 2.14 cells/HPF) was significantly higher than the GERD (2.77 ± 0.66 cells/HPF) and control groups (0.37 ± 0.08 cells/HPF) (P < 0.001). Additionally, the mean ± SEM of T lymphocytes in esophageal tissue of patients with EoE (24.39 ± 3.86 cells/HPF) were increased in comparison to the GERD (10.07 ± 2.65 cells/HPF) and control groups (3.17 ± 0.93 cells/HPF) (P < 0.001).
Conclusion: There is an increase in the number of esophageal T lymphocytes and regulatory T cells in patients with EoE compared to the GERD and control groups.
References
2. Rothenberg ME, Mishra A, Brandt EB, Hogan SP. Gastrointestinal eosinophils. Immunol Rev. 2001;179:139-55.
3. Simon D, Cianferoni A, Spergel JM, Aceves S, Holbreich M, Venter C, et al. Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity. Allergy. 2016;71:611-20.
4. Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med. 2004;351:940-1.
5. Rothenberg ME, Mishra A, Collins MH, Putnam PE. Pathogenesis and clinical features of eosinophilic esophagitis. J Allergy Clin Immunol. 2001;108:891-4.
6. Fuentebella J, Patel A, Nguyen T, Sanjanwala B, Berquist W, Kerner JA, et al. Increased number of regulatory T cells in children with eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2010;51:283-9.
7. Philpott H, Nandurkar S, Thien F, Gibson PR, Royce SG. Eosinophilic esophagitis: a clinicopathological review. Pharmacol Ther. 2015;146:12-22.
8. Bonis PA. The epidemiology and characteristics of eosinophilic esophagitis. Gastroenterol Hepatol. 2014;10:56.
9. Simon H-U, Straumann A. Immunopathogenesis of eosinophilic esophagitis. Digest Dis. 2014;32:11-4.
10. Simon D, Marti H, Heer P, Simon H-U, Braathen LR, Straumann A. Eosinophilic esophagitis is frequently associated with IgE-mediated allergic airway diseases. J Allergy Clin Immunol. 2005;115:1090.
11. Hawrylowicz CM. Regulatory T cells and IL-10 in allergic inflammation. J Exp Med. 2005;202:1459-63.
12. Sakaguchi S. Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol. 2004;22:531-62.
13. Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001;27:20.
14. Lal G, Zhang N, Van Der Touw W, Ding Y, Ju W, Bottinger EP, et al. Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation. J Immunol. 2009;182:259-73.
15. Zhang H, Kong H, Zeng X, Guo L, Sun X, He S. Subsets of regulatory T cells and their roles in allergy. J Transl Med. 2014;12:125.
16. Hill DA, Spergel JM. The immunologic mechanisms of eosinophilic esophagitis. Curr Allergy Asthma Rep. 2016;16:9.
17. Tatevian N, Gilger MA, Major AM, Davis CM. Increased esophageal regulatory T cells and eosinophil characteristics in children with eosinophilic esophagitis and gastroesophageal reflux disease. Ann Clin Lab Sci. 2009;39:99-107.
18. Stuck MC, Straumann A, Simon HU. Relative lack of T regulatory cells in adult eosinophilic esophagitis -no normalization after corticosteroid therapy. Allergy. 2011;66:705-7.
19. Liacouras CA, Spergel JM, Ruchelli E, Verma R, Mascarenhas M, Semeao E, et al. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol. 2005;3:1198-206.
20. Putnam PE. Evaluation of the child who has eosinophilic esophagitis. Immunol Allergy Clin North Am. 2009;29:1-10.
21. Rothenberg ME. Biology and treatment of eosinophilic esophagitis. Gastroenterology. 2009;137:1238-49.
22. Cookson W. The immunogenetics of asthma and eczema: a new focus on the epithelium. Nat Rev Immunol. 2004;4:978.
23. Simon D, Radonjic-Hösli S, Straumann A, Yousefi S, Simon HU. Active eosinophilic esophagitis is characterized by epithelial barrier defects and eosinophil extracellular trap formation. Allergy. 2015;70:443-52.
24. Islam SA, Luster AD. T cell homing to epithelial barriers in allergic disease. Nat Med. 2012;18:705.
25. Reekers R, Beyer K, Niggemann B, Wahn U, Freihorst J, KAP’P A, et al. The role of circulating food antigen-specific lymphocytes in food allergic children with atopic dermatitis. Br J Dermatol. 1996;135:935-41.
26. Beyer KCR, Birnbaum A, Benkov K, Pittman N, Sampson HA. Human milk-specific mucosal lymphocytes of the gastrointestinal tract display a TH2 cytokine profile. J Allergy Clin Immunol. 2002;109:707-13.
27. Faustino L, da Fonseca DM, Takenaka MC, Mirotti L, Florsheim EB, Guereschi MG, et al. Regulatory T cells migrate to airways via CCR4 and attenuate the severity of airway allergic inflammation. J Immunol. 2013, http://dx.doi.org/10.4049/jimmunol.1202354.
28. Sharma S, Watanabe S, Sivam A, Wang J, Neuwirth SJ, Perez RI, et al. Peripheral blood and tissue T regulatory cells in chronic rhinosinusitis. Am J Rhinol Allergy. 2012;26:371-9.
29. Hanafusa T, Matsui S, Murota H, Tani M, Igawa K, Katayama I. Increased frequency of skin-infiltrating FoxP3+ regulatory T cells as a diagnostic indicator of severe atopic dermatitis from cutaneous T cell lymphoma. Clin Exp Immunol. 2013;172:507-12.
30. Minshall EM, Leung DY, Martin RJ, Song YL, Cameron L, Ernst P, et al. Eosinophil-associated TGF-1 mRNA expression and airways fibrosis in bronchial asthma. Am J Respir Cell Mol Biol. 1997;17:326-33.
31. Ohno I, Lea R, Flanders K, Clark D, Banwatt D, Dolovich J, et al. Eosinophils in chronically inflamed human upper airway tissues express transforming growth factor beta 1 gene (TGF beta 1). J Clin Invest. 1992;89:1662-8.
32. Adel-Patient K, Wavrin S, Bernard H, Meziti N, Ah-Leung S, Wal JM. Oral tolerance and Treg cells are induced in BALB/c mice after gavage with bovine -lactoglobulin. Allergy. 2011;66:1312-21.
33. Murai M, Krause P, Cheroutre H, Kronenberg M. Regulatory Tcell stability and plasticity in mucosal and systemic immune systems. Mucosal Immunol. 2010;3:443.
34. da Silva Martins M, Piccirillo CA. Functional stability of Foxp3+ regulatory T cells. Trends Mol Med. 2012;18:454-62.
35. Baron U, Floess S, Wieczorek G, Baumann K, Grützkau A, Dong J, et al. DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3+ conventional T cells. Eur J Immunol. 2007;37:2378-89.
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