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Differences in phenotype, homing properties and suppressive activities of regulatory T cells induced by epicutaneous, oral or sublingual immunotherapy in mice sensitized to peanut
- Source :
- Cellular and Molecular Immunology
- Publication Year :
- 2016
- Publisher :
- Nature Publishing Group, 2016.
-
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.
- Subjects :
- 0301 basic medicine
Arachis
medicine.medical_treatment
Immunology
Receptors, Lymphocyte Homing
Administration, Oral
chemical and pharmacologic phenomena
Biology
Administration, Cutaneous
T-Lymphocytes, Regulatory
regulatory T cells
03 medical and health sciences
Chemokine receptor
0302 clinical medicine
Th2 Cells
Food allergy
medicine
Immunology and Allergy
Animals
Receptor
Desensitization (medicine)
mechanisms
Mice, Inbred BALB C
Sublingual Immunotherapy
FOXP3
hemic and immune systems
Immunotherapy
medicine.disease
allergy
Slit
030104 developmental biology
Infectious Diseases
Phenotype
Female
Immunization
immunotherapy
Lymph Nodes
Spleen
030215 immunology
Homing (hematopoietic)
Research Article
Nut and Peanut Hypersensitivity
Subjects
Details
- Language :
- English
- ISSN :
- 20420226 and 16727681
- Volume :
- 14
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Cellular and Molecular Immunology
- Accession number :
- edsair.doi.dedup.....a25cfc34829ae1d3ae33cd32eb1f99f0