The DNA methylation inhibitor 5-azacytidine increases regulatory T cells and alleviates airway inflammation in ovalbumin-sensitized mice

International Archives of Allergy and Immunology

Volumn 160, Issue 4, 2013, Pages 356-364

  Wu, Cheng Jang ^a   Yang, Chin Yu ^a   Chen, Yi Hsin ^a   Chen, Chun Ming ^a   Chen, Li Chen ^c   Kuo, Ming Ling ^a,b  

^a Graduate Institute of Rehabilitation Science   (Taiwan)

^b CHANG GUNG UNIVERSITY COLLEGE OF MEDICINE   (Taiwan)

^c CHANG GUNG MEMORIAL HOSPITAL   (Taiwan)

Author keywords

5 Azacytidine; Airway inflammation; Asthma; CD25+ cells; T regulatory cells; TH2 responses

Indexed keywords

AZACITIDINE; GAMMA INTERFERON; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G1; INTERLEUKIN 10; INTERLEUKIN 13; INTERLEUKIN 4; INTERLEUKIN 5; METHACHOLINE; OVALBUMIN; TRANSCRIPTION FACTOR FOXP3; CD4 ANTIGEN; INTERLEUKIN 2 RECEPTOR ALPHA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ASTHMA; B LYMPHOCYTE; CD25+ T LYMPHOCYTE; CD4+ CD25+ T LYMPHOCYTE; CONTROLLED STUDY; CYTOKINE PRODUCTION; DISEASE EXACERBATION; EOSINOPHILIA; FEMALE; FLOW CYTOMETRY; IN VIVO STUDY; LOEFFLER PNEUMONIA; LUNG LAVAGE; LYMPHOCYTE; LYMPHOCYTE SUBPOPULATION; MOUSE; NONHUMAN; PATHOGENESIS; PNEUMONIA; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; RESPIRATORY TRACT ALLERGY; RESPIRATORY TRACT INFLAMMATION; SENSITIZATION; SPLEEN CELL; TH2 CELL; ANIMAL TISSUE; CD8+ T LYMPHOCYTE; CELL HYPERPLASIA; CYTOKINE RELEASE; ENZYME LINKED IMMUNOSORBENT ASSAY; GOBLET CELL; HISTOLOGY; IMMUNOLOGICAL TOLERANCE; T CELL DEPLETION;

ANIMALS; ANTIGENS, CD4; ASTHMA; AZACITIDINE; BRONCHIAL HYPERREACTIVITY; BRONCHOALVEOLAR LAVAGE FLUID; DNA METHYLATION; EOSINOPHILIA; FORKHEAD TRANSCRIPTION FACTORS; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; INTERLEUKIN-13; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; INTERLEUKIN-4; INTERLEUKIN-5; METHACHOLINE CHLORIDE; MICE; MICE, INBRED BALB C; OVALBUMIN; RESPIRATORY SYSTEM; SPLEEN; T-LYMPHOCYTES, REGULATORY;

EID: 84869883694     PISSN: 10182438     EISSN: 14230097     Source Type: Journal    
DOI: 10.1159/000343030     Document Type: Article

References (35)

1. Akdis CA: Allergy and hypersensitivity: mechanisms of allergic disease. Curr Opin Immunol 2006; 18: 718-726.
2. Beasley R, Crane J, Lai CK, Pearce N: Prevalence and etiology of asthma. J Allergy Clin Immunol 2000; 105:S466-S472.
3. Busse WW, Lemanske RF Jr: Asthma. N Engl J Med 2001; 344: 350-362.
4. Romagnani S: The Th1/Th2 paradigm. Immunol Today 1997; 18: 263-266.
5. McKenzie AN: Regulation of T helper type 2 cell immunity by interleukin-4 and interleukin- 13. Pharmacol Ther 2000; 88: 143-151.
6. Nakajima H, Takatsu K: Role of cytokines in allergic airway inflammation. Int Arch Allergy Immunol 2007; 142: 265-273.
7. Chu EK, Drazen JM: Asthma: One hundred years of treatment and onward. Am J Respir Crit Care Med 2005; 171: 1202-1208.
8. Holgate ST, Polosa R: Treatment strategies for allergy and asthma. Nat Rev 2008; 8: 218-230.
9. Ryanna K, Stratigou V, Safinia N, Hawrylowicz C: Regulatory T cells in bronchial asthma. Allergy 2009; 64: 335-347.
10. Sakaguchi S, Sakaguchi N, Shimizu J, Yamazaki S, Sakihama T, Itoh M, Kuniyasu Y, Nomura T, Toda M, Takahashi T: Immunologic tolerance maintained by CD25+CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev 2001; 182: 18-32.
11. Xystrakis E, Boswell SE, Hawrylowicz CM: T regulatory cells and the control of allergic disease. Expert Opin Biol Ther 2006; 6: 121-133.
12. O'Garra A, Vieira P: Regulatory T cells and mechanisms of immune system control. Nat Med 2004; 10: 801-805.
13. Sakaguchi S: Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Ann Rev Immunol 2004; 22: 531-562.
14. Hori S, Nomura T, Sakaguchi S: Control of regulatory T cell development by the transcription factor Foxp3. Science 2003; 299: 1057-1061.
15. Kim HP, Leonard WJ: CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: a role for DNA methylation. J Exp Med 2007; 204: 1543-1551.
16. Baron U, Floess S, Wieczorek G, Baumann K, Grutzkau A, Dong J, Thiel A, Boeld TJ, Hoffmann P, Edinger M, Turbachova I, Hamann A, Olek S, Huehn J: DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3(+) conventional T cells. Eur J Immunol 2007; 37: 2378-2389.
17. Kaminskas E, Farrell AT, Wang YC, Sridhara R, Pazdur R: FDA drug approval summary: azacitidine (5-azacytidine, vidaza) for injectable suspension. Oncologist 2005; 10: 176-182.
18. Lal G, Zhang N, van der Touw W, Ding Y, Ju W, Bottinger EP, Reid SP, Levy DE, Bromberg JS: Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation. J Immunol 2009; 182: 259-273.
19. Wu CJ, Chen LC, Kuo ML: Attenuated Salmonella typhimurium reduces ovalbumininduced airway inflammation and T-helper type 2 responses in mice. Clin Exp Immunol 2006; 145: 116-122.
20. Brewer JP, Kisselgof AB, Martin TR: Genetic variability in pulmonary physiological, cellular, and antibody responses to antigen in mice. Am J Respir Crit Care Med 1999; 160: 1150-1156.
21. Burchell JT, Wikstrom ME, Stumbles PA, Sly PD, Turner DJ: Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells. Am J Physiol Lung Cell Mol Physiol 2009; 296:L307- L319.
22. Sumi T, Fukushima A, Fukuda K, Kumagai N, Nishida T, Takeuchi M, Taguchi O, Ueno H: Thymus-derived CD4+CD25+ T cells suppress the development of murine allergic conjunctivitis. Int Arch Allergy Immunol 2007; 143: 276-281.
23. Richardson B: DNA methylation and autoimmune disease. Clin Immunol 2003; 109: 72-79.
24. Brand S, Kesper DA, Teich R, Kilic-Niebergall E, Pinkenburg O, Bothur E, Lohoff M, Garn H, Pfefferle PI, Renz H: DNA methylation of TH1/TH2 cytokine genes affects sensitization and progress of experimental asthma. J Allergy Clin Immunol 2012;129:1602-1610.
25. Sanchez-Abarca LI, Gutierrez-Cosio S, Santamaria C, Caballero-Velazquez T, Blanco B, Herrero-Sanchez C, Garcia JL, Carrancio S, Hernandez-Campo P, Gonzalez FJ, Flores T, Ciudad L, Ballestar E, Del Canizo C, San Miguel JF, Perez-Simon JA: Immunomodulatory effect of 5-azacytidine (5-azac): potential role in the transplantation setting. Blood 2010; 115: 107-121.
26. Shi HZ, Qin XJ: CD4CD25 regulatory T lymphocytes in allergy and asthma. Allergy 2005; 60: 986-995.
27. Taylor A, Verhagen J, Akdis CA, Akdis M: T regulatory cells in allergy and health: a question of allergen specificity and balance. Int Arch Allergy Immunol 2004; 135: 73-82.
28. Itoh M, Takahashi T, Sakaguchi N, Kuni - yasu Y, Shimizu J, Otsuka F, Sakaguchi S: Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J Immunol 1999; 162: 5317-5326.
29. Jaffar Z, Sivakuru T, Roberts K: CD4+CD25+ T cells regulate airway eosinophilic inflammation by modulating the Th2 cell phenotype. J Immunol 2004; 172: 3842-3849.
30. Kearley J, Barker JE, Robinson DS, Lloyd CM: Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4+CD25+ regulatory T cells is interleukin 10 dependent. J Exp Med 2005; 202: 1539-1547.
31. Leech MD, Benson RA, De Vries A, Fitch PM, Howie SE: Resolution of Der p1-induced allergic airway inflammation is dependent on CD4+CD25+Foxp3+ regulatory cells. J Immunol 2007; 179: 7050-7058.
32. Fontenot JD, Gavin MA, Rudensky AY: Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003; 4: 330-336.
33. Zheng Q, Xu Y, Liu Y, Zhang B, Li X, Guo F, Zhao Y: Induction of Foxp3 demethylation increases regulatory CD4+CD25+ T cells and prevents the occurrence of diabetes in mice. J Mol Med 2009; 87: 1191-1205.
34. Kroetz DN, Deepe GS Jr: An aberrant thymus in CCR5-/- mice is coupled with an enhanced adaptive immune response in fungal infection. J Immunol 2011; 186: 5949-5955.
35. Tausendschon M, Dehne N, Brune B: Hypoxia causes epigenetic gene regulation in macrophages by attenuating jumonji histone demethylase activity. Cytokine 2011; 53: 256-262.