A synthetic glycodendropeptide induces methylation changes on regulatory T cells linked to tolerant responses in anaphylactic-mice

Frontiers in Immunology

Immunology

Clara Lebrón-Martín¹  Rafael Núñez¹  María J. Rodríguez¹  José A. Cañas¹  Cristobalina Mayorga²  María del Carmen Martín-Astorga³  María J. Torres⁴  Javier Ramos-Soriano⁵  Javier Rojo⁵ 

[1] Laboratory of Allergy, Allergy Research Group, Instituto de Investigación Biomédica de Málaga-Plataforma BIONAND (IBIMA-BIONAND), Málaga, Spain;Laboratory of Allergy, Allergy Research Group, Instituto de Investigación Biomédica de Málaga-Plataforma BIONAND (IBIMA-BIONAND), Málaga, Spain;Clinical Unit of Allergy, Hospital Regional Universitario de Málaga, Málaga, Spain;Laboratory of Allergy, Allergy Research Group, Instituto de Investigación Biomédica de Málaga-Plataforma BIONAND (IBIMA-BIONAND), Málaga, Spain;Department of Medicine, Universidad de Málaga (UMA), Málaga, Spain;Laboratory of Allergy, Allergy Research Group, Instituto de Investigación Biomédica de Málaga-Plataforma BIONAND (IBIMA-BIONAND), Málaga, Spain;Department of Medicine, Universidad de Málaga (UMA), Málaga, Spain;Clinical Unit of Allergy, Hospital Regional Universitario de Málaga, Málaga, Spain;Laboratory of Glycosystems, Institute of Chemical Research (IIQ), Centro Superior de Investigaciones Científicas (CSIC) - Universidad de Sevilla, Sevilla, Spain;

关键词: regulatory T cells;    methylation changes;    immunotherapy;    tolerance;    lipid transfer proteins;    food allergy;    glycodendropeptide;   

DOI  :  10.3389/fimmu.2023.1165852

 received in 2023-02-14, accepted in 2023-05-22,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionLipid transfer proteins (LTPs) are allergens found in a wide range of plant-foods. Specifically, Pru p 3, the major allergen of peach, is commonly responsible for severe allergic reactions. The need for new alternatives to conventional food allergy treatments, like restrictive diets, suggests allergen immunotherapy as a promising option. It has been demonstrated that sublingual immunotherapy (SLIT) with synthetic glycodendropeptides, such as D1ManPrup3, containing mannose and Pru p 3 peptides induced tolerance in mice and that the persistence of this effect depends on treatment dose (2nM or 5nM). Moreover, it produces changes associated with differential gene expression and methylation profile of dendritic cells, as well as phenotypical changes in regulatory T cells (Treg). However, there are no works addressing the study of epigenetic changes in terms of methylation in the cell subsets that sustain tolerant responses, Treg. Therefore, in this work, DNA methylation changes in splenic-Treg from Pru p 3 anaphylactic mice were evaluated.MethodsIt was performed by whole genome bisulphite sequencing comparing SLIT-D1ManPrup3 treated mice: tolerant (2nM D1ManPrup3), desensitized (5nM D1ManPrup3), and sensitized but not treated (antigen-only), with anaphylactic mice.ResultsMost of the methylation changes were found in the gene promoters from both SLIT-treated groups, desensitized (1,580) and tolerant (1,576), followed by the antigen-only (1,151) group. Although tolerant and desensitized mice showed a similar number of methylation changes, only 445 genes were shared in both. Remarkably, interesting methylation changes were observed on the promoter regions of critical transcription factors for Treg function like Stat4, Stat5a, Stat5b, Foxp3, and Gata3. In fact, Foxp3 was observed exclusively as hypomethylated in tolerant group, whereas Gata3 was only hypomethylated in the desensitized mice.DiscussionIn conclusion, diverse D1ManPrup3 doses induce different responses (tolerance or desensitization) in mice, which are reflected by differential methylation changes in Tregs.

【 授权许可】

Unknown   
Copyright © 2023 Núñez, Rodríguez, Lebrón-Martín, Martín-Astorga, Ramos-Soriano, Rojo, Torres, Cañas and Mayorga