title: Differences in phenotype, homing properties and suppressive activities of regulatory T cells induced by epicutaneous, oral or sublingual immunotherapy in mice sensitized to peanut.
abstract: Allergen-specific immunotherapy has been proposed as an attractive strategy to actively treat food allergy using the following three different immunotherapy routes: oral (OIT), sublingual (SLIT) and epicutaneous (EPIT) immunotherapy. Regulatory T cells (Tregs) have been shown to have a pivotal role in the mechanisms of immunotherapy. The aim of this study was to compare the phenotype and function of Tregs induced in peanut-sensitized BALB/c mice using these three routes of treatment. We show that although EPIT, OIT and SLIT were all able to effectively desensitize peanut-sensitized mice, they induced different subsets of Tregs. Foxp3+ Tregs were induced by the three treatment routes but with greater numbers induced by EPIT. EPIT and OIT also increased the level of LAP+ Tregs, whereas SLIT induced IL-10+ cells. The suppressive activity of EPIT-induced Tregs did not depend on IL-10 but required CTLA-4, whereas OIT acted through both mechanisms and SLIT was strictly dependent on IL-10. Moreover, the three routes influenced the homing properties of induced Tregs differently, with a larger repertoire of chemokine receptors expressed by EPIT-induced Tregs compared with OIT- and SLIT- induced cells, resulting in different protective consequences against allergen exposure. Furthermore, whereas OIT- or SLIT-induced Tregs lost their suppressive activities after treatment was discontinued, the suppressive activities of EPIT-induced Tregs were still effective 8 weeks after the end of treatment, suggesting the induction of a more long-lasting tolerance. In summary, EPIT, OIT and SLIT mediated desensitization through the induction of different subsets of Tregs, leading to important differences in the subsequent protection against allergen exposure and the possible induction of tolerance.
authors.affiliation: Research Department, DBV Technologies, Paris, 92220, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Dioszeghy
authors.affiliation: Research Department, DBV Technologies, Paris, 92220, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Mondoulet
authors.affiliation: Research Department, DBV Technologies, Paris, 92220, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Puteaux
authors.affiliation: Research Department, DBV Technologies, Paris, 92220, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Dhelft
authors.affiliation: Research Department, DBV Technologies, Paris, 92220, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Ligouis
authors.affiliation: Research Department, DBV Technologies, Paris, 92220, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Plaquet
authors.affiliation: Pédiatrie-Gastroentérologie, Université Paris Descartes &APHP-Hôpital Necker, Paris, 75743, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Dupont
authors.affiliation: Research Department, DBV Technologies, Paris, 92220, France.
authors.forename: Pierre-Henri
authors.initials: PH
authors.lastname: Benhamou
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D010367:Arachis / Q000009:adverse effects*; D005260:Female; D007114:Immunization; D008198:Lymph Nodes / Q000378:metabolism; D008807:Mice, Inbred BALB C; D000074924:Nut and Peanut Hypersensitivity / Q000276:immunology* / Q000652:urine*; D010641:Phenotype; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D063729:Sublingual Immunotherapy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016201:Receptors, Lymphocyte Homing