728:
Phenotypic changes and IDO over-expression in splenic dendritic cells after epicutaneous immunotherapy
Monday, March 5, 2018
South Hall A2 (Convention Center)
Benjamin Pelletier, Master degree, Lucie Mondoulet, PhD, Emilie Puteaux, Sylvain Tilleul, Fabien Delisle, Christophe Dupont, MD, PhD, Hugh A. Sampson, MD FAAAAI
RATIONALE: Epicutaneous immunotherapy (EPIT) was shown to induce Tregs expressing a variety of homing receptors, which are able to migrate and inhibit allergenic responses by antigen-presenting cells locally. This study aimed to characterize the effect of EPIT on splenic dendritic cells at the conclusion of immunotherapy and determine whether those changes are sustained.

METHODS: BALB/c mice were orally sensitized to peanut and treated with EPIT for 8 weeks or left untreated (Sham). Splenic dendritic cell subsets were characterized and activation of expression markers were analyzed by flow cytometry [MFI (median of fluorescence) for IDO, CD86, CD80 and MHC-II] immediately following treatment and 8 weeks after the end of the treatment.

RESULTS: Total splenic dendritic cells (CD11c+MHC-II+) exhibited higher MFI for IDO, MHC-II and CD80 following EPIT treatment compared to Sham (respectively 4632 vs 3565, 12978 vs 9447 (p˂0.05), 236.5 vs 212 (p˂0.01)). More specifically, only the resident CD11c+MHC-II+CD11b+CD8- subset demonstrated over-expression of those molecules compared to Sham (IDO: 4548 vs 3543, CD80: 370.5 vs 353, MHC-II: 13881 vs 9624 (p˂0.05)). Increases in IDO and MHC-II expressions (p˂0.01) was sustained 8 weeks after the end of treatment in CD11c+MHC-II+ and CD11c+MHC-II+CD11b+CD8-subsets (IDO MFI p˂0.01).

CONCLUSIONS: EPIT upregulated expression of IDO, CD80 and MHC-II in total splenic dendritic cells and resident CD11b+CD8-, IDO over-expression being sustained for 8 weeks off treatment in both populations. EPIT seems to specifically modify the CD11b+ CD8- subset, which might inhibit CD4+ proliferation by co-expression of IDO and MHC-II, and promote a tolerogenic environment.