Egg white peptide-based immunotherapy enhances vitamin A metabolism and induces RORγt+ regulatory T cells

Lozano‐Ojalvo, Daniel; Martínez‐Blanco, Mónica; Pérez-Rodríguez, Leticia; Molina, Elena; Peláez, Carmen; Requena, Teresa; López‐Fandiño, Rosina

doi:10.1016/j.jff.2018.11.012

Cited by 12 publications

(13 citation statements)

References 46 publications

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“…Quantitative microbiological analysis of samples was carried out in qPCR experiments analyzed using SYBR® green methodology in a ViiA7 Real-Time PCR System (Life Technologies, Carlsbad, CA, USA). Primers, amplicon size, and annealing temperature for Akkermansia , Bacteroides , Bifidobacterium , Enterobacteriaceae , Faecalibacterium , Lactobacillus , Enterococcus , Prevotella , Roseburia, Blautia coccoides-Eubacterium rectale Cluster XIVa, Ruminococcus Cluster IV, and Clostridium leptum subgroup specific cluster IV have been described previously 40 . For the analysis of B. fragilis and Bilophila we used the primers and PCR conditions described by Sjögren et al .…”

Section: Methodsmentioning

confidence: 99%

Lyso-Gb3 modulates the gut microbiota and decreases butyrate production

Aguilera-Correa

Madrazo-Clemente

Martínez-Cuesta

et al. 2019

Sci Rep

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Fabry disease is a rare X-linked lysosomal storage disorder resulting from deficient activity of α-galactosidase A, leading to the accumulation of glycosphingolipids such as globotriaosylsphingosine (lyso-Gb3). The gastrointestinal symptoms of this disease may be disabling, and the life expectancy of affected patients is shortened by kidney and heart disease. Our hypothesis was that lyso-Gb3 may modify the gut microbiota. The impact of a clinically relevant concentration of lyso-Gb3 on mono- or multispecies bacterial biofilms were evaluated. A complex bacterial community from the simulated transverse colon microbiota was studied using quantitative PCR to estimate different bacterial group concentrations and a HPLC was used to estimate short-chain fatty acids concentrations. We found that lyso-Gb3 increased the biofilm-forming capacity of several individual bacteria, including Bacteroides fragilis and significantly increased the growth of B. fragilis in a multispecies biofilm. Lyso-Gb3 also modified the bacterial composition of the human colon microbiota suspension, increasing bacterial counts of B. fragilis , among others. Finally, lyso-Gb3 modified the formation of short-chain fatty acids, leading to a striking decrease in butyrate concentration. Lyso-Gb3 modifies the biology of gut bacteria, favoring the production of biofilms and altering the composition and short-chain fatty-acid profile of the gut microbiota.

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Section: Methodsmentioning

confidence: 99%

Lyso-Gb3 modulates the gut microbiota and decreases butyrate production

Aguilera-Correa

Madrazo-Clemente

Martínez-Cuesta

et al. 2019

Sci Rep

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“…RNA extraction and qPCRassays were performed as described [13]. Relative gene expression was calculated by the 2 −∆∆CT method [19], normalising data to the expression of the Actb gene (coding for β-actin).…”

Section: Gene Expression Analysesmentioning

confidence: 99%

“…Immunotherapy with hydrolysates of ovalbumin (OVA) and egg white (EW) with pepsin was shown to stimulate tolerance development in BALB/c mice allergic to EW more effectively than treatment with the intact allergens, by virtue of the induction of Treg cells [12,13]. Hydrolysate-treated mice exhibit upregulated intestinal expression of Csf2, Aldh1a1, Aldh1a2, and Tgfb1, that are involved in the conversion of vitamin A into RA.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, tolerance parallels the development of Foxp3+ CD4+ T cells that simultaneously express RORγt, and it has been shown that RA is a characteristic component of local milieus that preferentially drive the induction and expansion of functionally suppressive RORγt+ Treg cells [14,15]. Interestingly, a Th2-skewed environment, such as that type of food allergy, was favourable to the promotion of vitamin A metabolism and to the induction of a Foxp3+ RORγt+ phenotype on CD4+ T cells by the hydrolysates [13].…”

Section: Introductionmentioning

confidence: 99%

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Ovalbumin-Derived Peptides Activate Retinoic Acid Signalling Pathways and Induce Regulatory Responses Through Toll-Like Receptor Interactions

et al. 2020

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This study investigates the potential of a hydrolysate of ovalbumin with pepsin (OP) to preclude Th2-type immunity by the enhancement of tolerogenic dendritic cells (DCs) and regulatory T (Treg) cells. Through Toll-like receptor (TLR) stimulation, OP enhances the retinoic acid pathway on DCs by means of the induction of aldehyde dehydrogenase enzymes and transforming growth factor beta (TGF-β), and it confers upon DC the ability to upregulate interleukin 10 (IL-10) as well as other tolerance-promoting mediators downstream of TRL signalling, such as IL-27, IL-33, Notch ligands, OX40L, and the transcription factors IRF4 and IRF8. OP-conditioned DCs induce the expansion of Foxp3+ and Tr1 cells in co-culture with CD4+ T cells. Furthermore, OP directly conditions CD4+ T cells from naïve mice, without the mediation of DCs, to express aldehyde dehydrogenase (ALDH) enzymes and, in the presence of the Th2 cytokine IL-4 and exogenous TGF-β, it enhances Foxp3 expression. It is noteworthy that, on CD4+ T cells isolated from egg-allergic mice, OP significantly enriches the levels of Foxp3+ and Foxp3+ RORγt+ CD4+ T cells. In conclusion, we show that food peptides may work, analogously to microbial-driven signals, through TLRs, to promote a tolerogenic phenotype on cells of the innate and adaptive immune system, a property that is further enhanced in the context of a Th2 cytokine-rich environment.

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“…While the mechanisms underlying their generation are not fully clear, involvement of antigens and metabolites derived from the gut microbiota, which stimulate epithelial production of retinoic acid (RA), has been proposed ( 3 , 6 ). In this respect, effective oral immunotherapy with peptides was also found to cause an increase in RORγt + Treg cells through the enhancement of vitamin A metabolism ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

Retinoic Acid Induces Functionally Suppressive Foxp3+RORγt+ T Cells In Vitro

et al. 2021

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IntroductionCD4+ T cells with regulatory function co-expressing Foxp3 and RORγt are linked to the development of oral tolerance towards innocuous food antigens in mice. This study aimed to discern the role played by IL-6 and retinoic acid (RA) in the in vitro generation of Foxp3+RORγt+ T cells and to investigate whether such cells have suppressive properties.MethodsCD4+CD25- T cells isolated from the spleen of BALB/c mice, were stimulated in the presence of IL-2 alone or together with TFG-β and different concentrations of IL-6 and/or RA. Percentage of Foxp3+, RORγt+, IL-17+, Foxp3+RORγt-, Foxp3+RORγt+, and Foxp3-RORγt+ T cells within the total CD4+ T cell population, production of cytokines (IL-10 and IL-17A) and gene expression (Foxp3, Rorc, Tgfb1, Il6, Il10, and Il17) were assessed at different time points. The phenotype and ability of cells generated from CD4+CD44-CD62L+ cells in the presence of RA to suppress effector T cell proliferation was assessed.ResultsTGF-β plus IL-6 induced the generation of Foxp3+ and double positive Foxp3+RORγt+ T cells to a higher extent than TGF-β alone at the beginning of the incubation period, although expression of Foxp3 subsequently declined. RA, added to TGF-β, increased Foxp3 and Rorc expression and Foxp3 and RORγt transcription and promoted the differentiation of Foxp3+RORγt- and Foxp3+RORγt+ cells that expressed and secreted IL-17. Foxp3+ T cells generated in vitro in presence of RA were functionally suppressive.ConclusionsUnder the influence of IL-2 and TGF-β, suppressive Foxp3+RORγt+ T cells that express and secrete IL-17 can be produced in vitro and RA further contributes to stabilize this phenotype.

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Egg white peptide-based immunotherapy enhances vitamin A metabolism and induces RORγt+ regulatory T cells

Cited by 12 publications

References 46 publications

Lyso-Gb3 modulates the gut microbiota and decreases butyrate production

Lyso-Gb3 modulates the gut microbiota and decreases butyrate production

Ovalbumin-Derived Peptides Activate Retinoic Acid Signalling Pathways and Induce Regulatory Responses Through Toll-Like Receptor Interactions

Retinoic Acid Induces Functionally Suppressive Foxp3+RORγt+ T Cells In Vitro

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