The Role of Regulatory T Cells in Epicutaneous Immunotherapy for Food Allergy

Abstract

In recent decades, a rapid increase in the prevalence of food allergies has led to extensive research on novel treatment strategies and their mechanisms. Mouse models have provided preliminary insights into the mechanism of epicutaneous immunotherapy (EPIT)-induced immune tolerance. In EPIT, antigen applied on the skin surface can be captured, processed, and presented in the lymph nodes (LNs) by Antigen-presenting cells (APCs). In the LNs, induction of regulatory T cells (Treg cells) requires both direct contact during antigen presentation and indirect mechanisms such as cytokines. Foxp3+CD62L+ Treg cells can exhibit the characteristics of hypomethylation of Foxp3 TSDR and Foxp3-LAP+ Treg cells, which increase the expression of surface tissue-specific homing molecules to exert further sustained systemic immune tolerance. Studies have shown that EPIT is a potential treatment for food allergies and can effectively induce immune tolerance, but its mechanism needs further exploration. Here, we review Treg cells’ role in immune tolerance induced by EPIT and provide a theoretical basis for future research directions, such as the mechanism of EPIT and the development of more effective EPIT treatments.

Immunology of allergen immunotherapy

“…An ex vivo analysis among patients following EPIT therapy demonstrated a reduction in the frequencies of allergen-specific type 2 cells, specifically CD154 + IL4 + and CD154 + IL-13 + cells and an increase in the frequency of CD154 + IL10 + cells [ 100 ]. In hallmarking a shift towards a regulatory phenotype, EPIT has been associated with an induction of CD25 + Foxp3 + CD4 T cells in lymphoid tissue [ 87 , 123 , 124 ]. Use of an anti-CD25 antibody was able to reverse induction of Tregs with consequent eosinophilic infiltration of the esophagus in peanut-sensitized mice, highlighting the role of Tregs in establishing peripheral non-responsiveness [ 125 ].…”

Allergen-specific immunotherapy in allergic rhinitis

“…Существует по крайней мере пять способов введения аллергенов при АСИТ: подкожный [7-9], подъязычный [10][11][12], оральный [13][14][15], эпикутанный [16,17] и внутрилимфатический [18,19]. В настоящее время документировано и апробировано два пути введения аллергенов для применения в практике: подкожный [7] и подъязычный [10].…”

“…Одновременно представляет-ся возможность применять толерогенные адъюванты [16]. Другая модификация метода заключается в аппликации кожных сменных патчей для ежедневной поддерживающей дозы аллергенов [17]. Поскольку эпидермис не васкуляризирован, риск системных побочных реакций существенно ниже, чем при других путях введения аллергенов.…”

Short-Chain Fatty Acids Augment Differentiation and Function of Human Induced Regulatory T Cells

“…The contribution of reduced Treg function to disease development has also been demonstrated for allergic disorders, such as atopic asthma, allergic rhinitis, food allergies, atopic dermatitis, allergic conjunctivitis, and others [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. Additionally, in this case, various types of therapeutic interventions involving Tregs have been proposed [ 12 , 13 , 14 , 15 , 16 , 17 ].…”