Antigen Uptake by Langerhans Cells Is Required for the Induction of Regulatory T Cells and the Acquisition of Tolerance During Epicutaneous Immunotherapy in OVA-Sensitized Mice

Frontiers in Immunology
Vincent DioszeghyHugh A Sampson

Abstract

The skin is a major immunologic organ that may induce protection, sensitization or tolerance. Epicutaneous immunotherapy (EPIT) has been proposed as an attractive strategy to actively treat food allergy and has been shown to induce tolerance in sensitized mice through the induction of Foxp3+ regulatory T cells (Tregs), especially CD62L+ Tregs. Among immune cells in the skin, dendritic cells are key players in antigen-specific immune activation or regulation. The role of different populations of skin DCs in tolerance induction remains to be elucidated. Using OVA-sensitized BALB/c mice, we demonstrated that the application of a patch containing OVA-A647 to the skin resulted in allergen uptake by Langerhans cells (LCs) and CD11b+ dermal cDC2 and subsequent migration into skin draining lymph nodes. These 2 populations induced Foxp3 expression in CD4+ cells in vitro. Only LCs induced LAP+ cells and CD62L+ Tregs. Using Langerin-eGFP-DTR mice, we analyzed the role of LCs in the mechanisms of tolerance induction by EPIT in vivo. Following complete depletion of LCs, a dramatic decrease in the number of OVA+ DCs and OVA+ CD11b+ dermal cDC2 was observed in skin draining lymph nodes 48 h after epicutaneous application. Likewise, 2 weeks of...Continue Reading

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Citations

Jan 23, 2019·International Immunology·Tetsuya HondaKenji Kabashima
Mar 14, 2019·Expert Review of Clinical Immunology·Alexandra LangloisPhilippe Bégin
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Oct 1, 2020·Allergy·Benjamin PelletierPierre-Louis Hervé
Nov 24, 2020·Frontiers in Immunology·Ann-Marie Malby SchoosWillem van de Veen
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Jul 27, 2021·Frontiers in Immunology·Guirong LiuHuilian Che
Aug 28, 2021·International Journal of Molecular Sciences·Laura PasseriSilvia Gregori

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Methods Mentioned

BETA
biopsies
flow cytometry

Software Mentioned

Viaskins
FlowJo
GraphPad Prism

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