381:
Unique epigenetic signature in T cell compartment after epicutaneous immunotherapy in peanut sensitized mice
Sunday, March 4, 2018
South Hall A2 (Convention Center)
Lucie Mondoulet, PhD, Vincent Dioszeghy, PhD, Camille Plaquet, Elodie Roche, Veronique Dhelft, Florence Busato, Christophe Dupont, MD, PhD, Hugh A. Sampson, MD FAAAAI, Jorg Tost, PhD
RATIONALE:

Epicutaneous immunotherapy (EPIT) induces naïve Tregs, which play a crucial role in the bystander effect identified in a model of food allergic mice. Previously, EPIT was shown to alter epigenetic modifications and expression of Th2 and Tregs without influencing the expression of Th1 in peanut-sensitized mice. This study investigates methylation modifications occurring in specific T cell compartments.

METHODS:

Mice were orally sensitized to peanut and then treated with EPIT or non-treated. Mice were sacrificed at the end of treatment or 8 weeks after the end of immunotherapy. Regulatory T cells (CD62L+Foxp3+ and CD62L-Foxp3+) were sorted directly from the spleen and Th2 and Th1 cells were purified after a short in vitro reactivation of splenocytes. DNA methylation at Gata3 promoter and Foxp3 CNS2 was analysed in all sorted cells by pyrosequencing.

RESULTS:

Epicutaneous immunotherapy did not modify proportions of Th1 and Th2 cells in the spleen. The hypermethylation of CpG islands of Gata3 only occurred in Th2 cells for EPIT-treated mice at the end of immunotherapy and was sustained 8 weeks later (p<0.05 vs Sham). In parallel, significant hypomethylation was observed in the Foxp3 CpG islands of naïve Tregs only (p<0.05), not effector Tregs, at the end of EPIT, and persisted for 8 weeks following the end of treatment (p<0.001).

CONCLUSIONS:

The unique epigenetic signature of EPIT is confirmed at cellular level for Gata3 (Th2) and Foxp3 (naïve Tregs), suggesting the induction of tolerance and prevention of further sensitization. Foxp3 hypomethylation occurring only on naïve Tregs underlines the crucial role of EPIT-induced naïve Tregs.