7 research outputs found
A synthetic glycodendropeptide induces methylation changes on regulatory T cells linked to tolerant responses in anaphylactic-mice
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
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Social relationships, neighbourhood poverty and cumulative biological risk: findings from a multi-racial US urban community.
Prior research has established associations between neighbourhood poverty and cumulative biological risk (CBR). CBR is conceptualized as indicative of the effects of stress on biological functioning, and is linked with increased morbidity and mortality. Studies suggest that supportive social relationships may be health protective, and may erode under conditions of poverty. This study examines whether social relationships are inversely associated with CBR and whether associations between neighbourhood poverty and CBR are mediated through social relationships. Data were from a stratified probability sample community survey (n=919) of residents of Detroit, Michigan, USA (2002-2003) and from the 2000 US Census. The outcome variable, CBR, included anthropometric and clinical measures. Independent variables included four indicators of social relationships: social support, neighbourhood satisfaction, social cohesion and neighbourhood participation. Multilevel models were used to test both research questions, with neighbourhood poverty and social relationships included at the block group level, and social relationships also included at the individual level, to disentangle individual from neighbourhood effects. Findings suggest some associations between social relationships and CBR after accounting for neighbourhood poverty and individual characteristics. In models that accounted for all indicators of social relationships, individual-level social support was associated with greater CBR (β=0.12, p=0.04), while neighbourhood-level social support was marginally significantly protective of CBR (within-neighbourhood: β=-0.36, p=0.06; between-neighbourhood: β=-0.24, p=0.06). In contrast, individual-level neighbourhood satisfaction was protective of CBR (β=-0.10, p=0.02), with no within-neighbourhood (β=0.06, p=0.54) or between-neighbourhood association (β=-0.04, p=0.38). Results indicate no significant association between either social cohesion or neighbourhood participation and CBR. Associations between neighbourhood poverty and CBR were not mediated by social relationships. These findings suggest that neighbourhood-level social support and individual-level neighbourhood satisfaction may be health protective and that neighbourhood poverty, social support and neighbourhood satisfaction are associated with CBR through independent pathways