Article (Scientific journals)
Azacytidine mitigates experimental sclerodermic chronic graft-versus-host disease
Fransolet, Gilles; Ehx, Grégory; SOMJA, Joan et al.
2016In Journal of Hematology and Oncology, 9, p. 53
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Keywords :
AZA; DAC; Tregs; Azacytidine; Decitabine; Regulatory T cells; GVHD; Graft-versus-host disease; Chronic GVHD; Sclerodermic chronic GVHD
Abstract :
[en] Background <br />Previous studies have demonstrated that regulatory T cells (Tregs) play a protective role in the pathogenesis of chronic graft-versus-host disease (cGVHD). Tregs constitutively express the gene of the transcription factor Foxp3 whose CNS2 region is heavily methylated in conventional CD4+ T cells (CD4+Tconvs) but demethylated in Tregs. <br />Methods <br />Here, we assessed the impact of azacytidine (AZA) on cGVHD in a well-established murine model of sclerodermic cGVHD (B10.D2 (H-2d) → BALB/cJ (H-2d)). <br />Results <br />The administration of AZA every 48 h from day +10 to day +30 at the dose of 0.5 mg/kg or 2 mg/kg mitigated chronic GVHD. Further, AZA-treated mice exhibited higher blood and thymic Treg frequencies on day +35, as well as higher demethylation levels of the Foxp3 enhancer and the IL-2 promoter in splenocytes at day +52. Interestingly, Tregs from AZA-treated mice expressed more frequently the activation marker CD103 on day +52. AZA-treated mice had also lower counts of CD4+Tconvs and CD8+ T cells from day +21 to day +35 after transplantation, as well as a lower proportion of CD4+Tconvs expressing the Ki67 antigen on day +21 demonstrating an anti-proliferating effect of the drug on T cells. <br />Conclusions <br />Our results indicate that AZA prevented sclerodermic cGVHD in a well-established murine model of cGVHD. These data might serve as the basis for a pilot study of AZA administration for cGVHD prevention in patients at high risk for cGVHD.
Disciplines :
Hematology
Author, co-author :
Fransolet, Gilles  ;  Université de Liège > GIGA-R : Hématologie
Ehx, Grégory   ;  Université de Liège > GIGA-R : Hématologie
SOMJA, Joan ;  Centre Hospitalier Universitaire de Liège - CHU > Service dermatopathologie
Delens, Loïc ;  Université de Liège > GIGA-R : Hématologie
Hannon, Muriel ;  Université de Liège > GIGA-R : Hématologie
Muller, Joséphine ;  Université de Liège > GIGA-R : Hématologie
DUBOIS, Sophie ;  Centre Hospitalier Universitaire de Liège - CHU > Service d'hématologie clinique
Drion, Pierre ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R:Méth. expér.des anim. de labo et éth. en expér. anim.
CAERS, Jo  ;  Centre Hospitalier Universitaire de Liège - CHU > Service d'hématologie clinique
Humblet-Baron, Stéphanie;  Katholieke Universiteit Leuven - KUL > Department of Microbiology and Immunology > Translational Immunology Laboratory
DELVENNE, Philippe ;  Centre Hospitalier Universitaire de Liège - CHU > Service d'anatomie et cytologie pathologiques
BEGUIN, Yves  ;  Centre Hospitalier Universitaire de Liège - CHU > Service d'hématologie clinique
Conteduca, Giuseppina  ;  Université de Liège > GIGA-R : Hématologie
BARON, Frédéric   ;  Centre Hospitalier Universitaire de Liège - CHU > Service d'hématologie clinique
More authors (4 more) Less
 These authors have contributed equally to this work.
Language :
English
Title :
Azacytidine mitigates experimental sclerodermic chronic graft-versus-host disease
Publication date :
04 July 2016
Journal title :
Journal of Hematology and Oncology
eISSN :
1756-8722
Publisher :
BioMed Central
Volume :
9
Pages :
53
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 14 July 2016

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