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Papers by Camille Plaquet

Research paper thumbnail of Differences in phenotype, homing properties and suppressive activities of regulatory T cells induced by epicutaneous, oral or sublingual immunotherapy in mice sensitized to peanut

Cellular & Molecular Immunology, 2016

Allergen-specific immunotherapy has been proposed as an attractive strategy to actively treat foo... more 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.Cellular & Molecular Immunology advance online publication, 11 April 2016; doi:10.1038/cmi.2016.14.

Research paper thumbnail of No Impact of Filaggrin Deficiency on Epit Efficacy in a Murine Model

Journal of Allergy and Clinical Immunology, 2016

Research paper thumbnail of Three Complementary Pathways Characterize the Suppressive Properties of Epit-Induced Tregs

Journal of Allergy and Clinical Immunology, 2016

Research paper thumbnail of Epit Prevents from the Induction of Anaphylaxis to Further Allergens: Role of Naive Tregs

Journal of Allergy and Clinical Immunology, 2016

Research paper thumbnail of Sustainability of Phenotype and Suppressive Activities of Tregs after Discontinuation of Epit but Not of OIT or Slit in Peanut Sensitized Mice

Journal of Allergy and Clinical Immunology, 2016

Research paper thumbnail of Epicutaneous but Not Oral Immunotherapy Leads to Sustainable GATA-3 Hypermethylation and Foxp3 Hypomethylation in Peanut Sensitized Mice

Journal of Allergy and Clinical Immunology, 2016

Research paper thumbnail of L’immunothérapie épicutanée induit des lymphocytes T régulateur ayant un tropisme digestif adapté au traitement de l’allergie alimentaire

Revue Française d'Allergologie, 2015

Research paper thumbnail of Epicutaneous Immunotherapy Prevents from Induction of Anaphylaxis to Further Allergens

Journal of Allergy and Clinical Immunology, 2015

Research paper thumbnail of Epigenetic Changes Following Epicutaneous Immunotherapy in Peanut Sensitized Mice

Journal of Allergy and Clinical Immunology, 2015

Research paper thumbnail of Larger and Stronger Expression of Tregs Gut Homing Receptors with Epicutaneous Than with Sublingual or Oral Immunotherapy

Journal of Allergy and Clinical Immunology, 2015

Research paper thumbnail of Long Term Protection Against New Sensitization After Milk-Epit In Mice Sensitized To Milk Is Mediated By Tregs

Journal of Allergy and Clinical Immunology, 2014

Research paper thumbnail of Epicutaneous Immunotherapy-Induced Regulatory T Cells Could Migrate To More Various Sites Of Allergen Exposure Compared To Sublingual Or Subcutaneous Immunotherapy In Mice Sensitized To Peanut

Journal of Allergy and Clinical Immunology, 2014

Background Allergen-specific immunotherapy favours immune deviation from a Th2 to a Th1 response ... more Background Allergen-specific immunotherapy favours immune deviation from a Th2 to a Th1 response and increases the number of regulatory T cells (Tregs). Epicutaneous immunotherapy (EPIT) of sensitized mice decreases the clinical and the allergen-specific Th2 responses and increases local and peripheral Foxp3 + Tregs. Objective To investigate the role of Tregs in EPIT and characterize their phenotype and maintenance following EPIT. Methods Tregs were investigated using in vivo depletion or adoptive transfer into BALB/c mice. Tregs were depleted using anti-CD25 antibody injection during EPIT, and allergenspecific responses were compared with Sham, EPIT alone and na€ ıve mice. To demonstrate that Tregs can mediate protection by their own, and to study their maintenance following the end of EPIT, CD25 + CD4 + Tregs isolated from mice just after or 8 weeks after EPIT were transferred into peanut-sensitized mice. Foxp3-IRES-mRFP mice were transferred with EPIT-induced Tregs to analyse the induction of host Tregs. Results The anti-CD25 antibody injection to EPIT mice abrogated the induction of Tregs in spleen and the expression of Foxp3 in oesophagus. This resulted in levels of peanutinduced eosinophilic infiltration in oesophagus similar to Sham and significantly higher than EPIT. Whereas the transfer of Tregs from Sham-treated mice demonstrated no effect, the transfer of Tregs isolated just after EPIT prevented peanut-induced eosinophil infiltration and eotaxin expression and induced Foxp3 in oesophagus. The transfer of Tregs isolated 8 weeks after EPIT suppressed allergen-specific responses as efficiently as did Tregs isolated just after EPIT and increased spleen Foxp3 + CD25 + CD4 + cells similarly. The use of reporter mice demonstrated an increase in host Tregs. Conclusions These results confirm the Tregs-mediated mechanism of EPIT and demonstrate the persistence of efficient Tregs during a long period of time after treatment cessation. This suggests that EPIT induces long-term tolerance in peanut-sensitized mice.

Research paper thumbnail of Epicutaneous Immunotherapy Induces Epigenetic Changes In Sensitized Mice

Journal of Allergy and Clinical Immunology, 2014

Research paper thumbnail of Specific epicutaneous immunotherapy prevents sensitization to new allergens in a murine model

Journal of Allergy and Clinical Immunology, 2015

Background: Allergy to cow's milk increases the risk of sensitization to other foods in young chi... more Background: Allergy to cow's milk increases the risk of sensitization to other foods in young children. Objectives: We sought to evaluate the effect of early epicutaneous immunotherapy (EPIT) on further sensitization to peanut or house dust mite (HDM) in a murine model of sensitization to cow's milk. Methods: BALB/c mice orally sensitized to milk were epicutaneously treated with a Viaskin patch (DBV Technologies) loaded with milk proteins for 8 weeks. Mice were then sensitized to peanut or HDM. After sensitization to peanut, mice were exposed to a peanut regimen known to induce eosinophilic esophageal inflammation. After sensitization to HDM, mice were challenged with aerosols to HDM, and airway hyperresponsiveness was evaluated by using plethysmography. Humoral response was also analyzed. The role of regulatory T (Treg) cells was evaluated by adoptively transferring Treg cells from milk EPIT-treated mice to naive mice before sensitization to peanut. Protection against anaphylaxis was also investigated. Methylation of the promoter region of transcription factors was analyzed by using PCR assays. Results: In milk-sensitized mice specific EPIT prevented further sensitization to peanut or HDM. EPIT significantly modified the humoral response, reduced T H 2 cytokine levels, decreased eosinophilic esophageal infiltration, and suppressed airway hyperresponsiveness. The protective effect was sustained over 2 months. Moreover, the adoptive transfer of milk EPIT Treg cells completely prevented sensitization to peanut and peanutinduced anaphylaxis. Milk EPIT enhanced methylation of the GATA-3 promoter region. Conclusions: Our results showed that EPIT influences the natural history of allergy and reduces the risk of further sensitization through a Treg cell-dependent mechanism. (J Allergy Clin Immunol 2014;nnn:nnn-nnn.)

Research paper thumbnail of Differences in phenotype, homing properties and suppressive activities of regulatory T cells induced by epicutaneous, oral or sublingual immunotherapy in mice sensitized to peanut

Cellular & Molecular Immunology, 2016

Allergen-specific immunotherapy has been proposed as an attractive strategy to actively treat foo... more 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.Cellular & Molecular Immunology advance online publication, 11 April 2016; doi:10.1038/cmi.2016.14.

Research paper thumbnail of No Impact of Filaggrin Deficiency on Epit Efficacy in a Murine Model

Journal of Allergy and Clinical Immunology, 2016

Research paper thumbnail of Three Complementary Pathways Characterize the Suppressive Properties of Epit-Induced Tregs

Journal of Allergy and Clinical Immunology, 2016

Research paper thumbnail of Epit Prevents from the Induction of Anaphylaxis to Further Allergens: Role of Naive Tregs

Journal of Allergy and Clinical Immunology, 2016

Research paper thumbnail of Sustainability of Phenotype and Suppressive Activities of Tregs after Discontinuation of Epit but Not of OIT or Slit in Peanut Sensitized Mice

Journal of Allergy and Clinical Immunology, 2016

Research paper thumbnail of Epicutaneous but Not Oral Immunotherapy Leads to Sustainable GATA-3 Hypermethylation and Foxp3 Hypomethylation in Peanut Sensitized Mice

Journal of Allergy and Clinical Immunology, 2016

Research paper thumbnail of L’immunothérapie épicutanée induit des lymphocytes T régulateur ayant un tropisme digestif adapté au traitement de l’allergie alimentaire

Revue Française d'Allergologie, 2015

Research paper thumbnail of Epicutaneous Immunotherapy Prevents from Induction of Anaphylaxis to Further Allergens

Journal of Allergy and Clinical Immunology, 2015

Research paper thumbnail of Epigenetic Changes Following Epicutaneous Immunotherapy in Peanut Sensitized Mice

Journal of Allergy and Clinical Immunology, 2015

Research paper thumbnail of Larger and Stronger Expression of Tregs Gut Homing Receptors with Epicutaneous Than with Sublingual or Oral Immunotherapy

Journal of Allergy and Clinical Immunology, 2015

Research paper thumbnail of Long Term Protection Against New Sensitization After Milk-Epit In Mice Sensitized To Milk Is Mediated By Tregs

Journal of Allergy and Clinical Immunology, 2014

Research paper thumbnail of Epicutaneous Immunotherapy-Induced Regulatory T Cells Could Migrate To More Various Sites Of Allergen Exposure Compared To Sublingual Or Subcutaneous Immunotherapy In Mice Sensitized To Peanut

Journal of Allergy and Clinical Immunology, 2014

Background Allergen-specific immunotherapy favours immune deviation from a Th2 to a Th1 response ... more Background Allergen-specific immunotherapy favours immune deviation from a Th2 to a Th1 response and increases the number of regulatory T cells (Tregs). Epicutaneous immunotherapy (EPIT) of sensitized mice decreases the clinical and the allergen-specific Th2 responses and increases local and peripheral Foxp3 + Tregs. Objective To investigate the role of Tregs in EPIT and characterize their phenotype and maintenance following EPIT. Methods Tregs were investigated using in vivo depletion or adoptive transfer into BALB/c mice. Tregs were depleted using anti-CD25 antibody injection during EPIT, and allergenspecific responses were compared with Sham, EPIT alone and na€ ıve mice. To demonstrate that Tregs can mediate protection by their own, and to study their maintenance following the end of EPIT, CD25 + CD4 + Tregs isolated from mice just after or 8 weeks after EPIT were transferred into peanut-sensitized mice. Foxp3-IRES-mRFP mice were transferred with EPIT-induced Tregs to analyse the induction of host Tregs. Results The anti-CD25 antibody injection to EPIT mice abrogated the induction of Tregs in spleen and the expression of Foxp3 in oesophagus. This resulted in levels of peanutinduced eosinophilic infiltration in oesophagus similar to Sham and significantly higher than EPIT. Whereas the transfer of Tregs from Sham-treated mice demonstrated no effect, the transfer of Tregs isolated just after EPIT prevented peanut-induced eosinophil infiltration and eotaxin expression and induced Foxp3 in oesophagus. The transfer of Tregs isolated 8 weeks after EPIT suppressed allergen-specific responses as efficiently as did Tregs isolated just after EPIT and increased spleen Foxp3 + CD25 + CD4 + cells similarly. The use of reporter mice demonstrated an increase in host Tregs. Conclusions These results confirm the Tregs-mediated mechanism of EPIT and demonstrate the persistence of efficient Tregs during a long period of time after treatment cessation. This suggests that EPIT induces long-term tolerance in peanut-sensitized mice.

Research paper thumbnail of Epicutaneous Immunotherapy Induces Epigenetic Changes In Sensitized Mice

Journal of Allergy and Clinical Immunology, 2014

Research paper thumbnail of Specific epicutaneous immunotherapy prevents sensitization to new allergens in a murine model

Journal of Allergy and Clinical Immunology, 2015

Background: Allergy to cow's milk increases the risk of sensitization to other foods in young chi... more Background: Allergy to cow's milk increases the risk of sensitization to other foods in young children. Objectives: We sought to evaluate the effect of early epicutaneous immunotherapy (EPIT) on further sensitization to peanut or house dust mite (HDM) in a murine model of sensitization to cow's milk. Methods: BALB/c mice orally sensitized to milk were epicutaneously treated with a Viaskin patch (DBV Technologies) loaded with milk proteins for 8 weeks. Mice were then sensitized to peanut or HDM. After sensitization to peanut, mice were exposed to a peanut regimen known to induce eosinophilic esophageal inflammation. After sensitization to HDM, mice were challenged with aerosols to HDM, and airway hyperresponsiveness was evaluated by using plethysmography. Humoral response was also analyzed. The role of regulatory T (Treg) cells was evaluated by adoptively transferring Treg cells from milk EPIT-treated mice to naive mice before sensitization to peanut. Protection against anaphylaxis was also investigated. Methylation of the promoter region of transcription factors was analyzed by using PCR assays. Results: In milk-sensitized mice specific EPIT prevented further sensitization to peanut or HDM. EPIT significantly modified the humoral response, reduced T H 2 cytokine levels, decreased eosinophilic esophageal infiltration, and suppressed airway hyperresponsiveness. The protective effect was sustained over 2 months. Moreover, the adoptive transfer of milk EPIT Treg cells completely prevented sensitization to peanut and peanutinduced anaphylaxis. Milk EPIT enhanced methylation of the GATA-3 promoter region. Conclusions: Our results showed that EPIT influences the natural history of allergy and reduces the risk of further sensitization through a Treg cell-dependent mechanism. (J Allergy Clin Immunol 2014;nnn:nnn-nnn.)