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Epicutaneous but Not Oral Immunotherapy Leads to Sustainable GATA-3 Hypermethylation and Foxp3 Hypomethylation in Peanut Sensitized Mice
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
Jorg Tost, PhD, Lucie Mondoulet, PhD, Emilie Puteaux, Florence Busato, Mélanie Ligouis, Véronique Dhelft, Camille Plaquet, Christophe Dupont, MD PhD, Pierre-Henri Benhamou, MD
Rationale:

Epicutaneous immunotherapy (EPIT) is a safe method for treating food allergies and animal models show that protection is sustainable. Previously, EPIT has been shown to alter epigenetic modifications and expression of Th2 and Tregs without influencing the expression of Th1 in peanut-sensitized mice. This study investigates the kinetics of epigenetic modifications underlying the therapeutic effect of EPIT and its persistence compared to oral immunotherapy (OIT).

Methods:

Mice were orally sensitized to peanut and then treated by EPIT or OIT or non-treated (sham). Mice were sacrificed every 2 weeks during the immunotherapeutic protocols and also 8 weeks after the end of immunotherapy. DNA methylation was analysed in sorted CD4 T cells from spleen and blood by pyrosequencing.

Results:

 In spleen and blood CD4 T-cells, significant hypermethylation of CpG islands of Gata3 was observed from the 4th week of EPIT and persisted following the end of treatment. This modification was not observed with OIT. In parallel, significant hypomethylation was observed in the Foxp3 CpG islands in spleen and blood CD4 T-cells from the 4th week of EPIT compared to Sham, which persisted following the end of treatment. For OIT, a similar level of hypomethylation was observed only in spleen CD4 T cells but was not sustained following the end of treatment.

Conclusions:

The hypermethylation of Th2 transcription factor appears to be a specific trait of EPIT-induced immunomodulation. Foxp3 hypomethylation occurred with both EPIT and OIT, but proved sustainable only with EPIT, explaining the sustainability of EPIT protection in the mouse model.