DNA methylation of TH1/TH2 cytokine genes affects sensitization and progress of experimental asthma.
J Allergy Clin Immunol
; 129(6): 1602-10.e6, 2012 Jun.
Article
em En
| MEDLINE
| ID: mdl-22277202
ABSTRACT
BACKGROUND:
Epigenetic changes in DNA methylation have recently been demonstrated to be involved in effector T-cell polarization, resulting in differential secretion of T(H)1 and T(H)2 cytokines. However, the contribution to the development of a chronic inflammatory phenotype remains still unclear.OBJECTIVE:
We sought to investigate changes in DNA methylation in marker genes of T-cell subsets during allergen sensitization/challenge and their influence on the development of an allergic airway inflammatory response.METHODS:
The relationship between changes in DNA methylation and phenotype development were examined in a well-established model of experimental asthma. DNA methylation was investigated at genomic loci associated with T(H)1 (IFNG promoter) or T(H)2 (conserved noncoding sequence 1 [CNS1]) cytokine production by using bisulfite pyrosequencing.RESULTS:
Analysis of CD4(+) T cells revealed a significant increase in DNA methylation at the IFNG promoter after allergen sensitization/challenge, which correlated with decreased IFN-γ cytokine expression, whereas only minor changes were observed at the CNS1 locus. Furthermore, the increase in DNA methylation at the IFNG promoter could be reversed with a DNA methyltransferase (DNMT) inhibitor in vitro and in vivo with beneficial effects on sensitization status and allergic phenotype. The specific importance of the DNA methylation status in CD4(+) T cells could be confirmed by using adoptive transfer experiments.CONCLUSION:
We here report the novel finding that epigenetic regulation in T cells contributes to the development of experimental asthma and can be targeted pharmacologically.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Asma
/
Citocinas
/
Células Th2
/
Células Th1
/
Metilação de DNA
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article