Dataset Information

Immunomodulatory Response of Toll-like Receptor Ligand-Peptide Conjugates in Food Allergy.

ABSTRACT: Covalent conjugation of allergens to toll-like receptor (TLR) agonists appears to be a powerful strategy for the development of safety compounds for allergen-specific immunomodulatory response toward tolerance in allergy. In this work, we have synthesized two family of ligands, an 8-oxoadenine derivative as a ligand for TLR7 and a pyrimido[5,4-b]indole as a ligand for TLR4, both conjugated with a T-cell peptide of Pru p 3 allergen, the lipid transfer protein (LTP) responsible for LTP-dependent food allergy. These conjugates interact with dendritic cells, inducing their specific maturation, T-cell proliferation, and cytokine production in peach allergic patients. Moreover, they increased the Treg-cell frequencies in these patients and could induce the IL-10 production. These outcomes were remarkable in the case of the TLR7 ligand conjugated with Pru p 3, opening the door for the potential application of these allergen-adjuvant systems in food allergy immunotherapy.

SUBMITTER: Losada Mendez J

PROVIDER: S-EPMC8609526 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Immunomodulatory Response of Toll-like Receptor Ligand-Peptide Conjugates in Food Allergy.

Losada Méndez Jorge J Palomares Francisca F Gómez Francisca F Ramírez-López Pedro P Ramos-Soriano Javier J Torres Maria Jose MJ Mayorga Cristobalina C Rojo Javier J

ACS chemical biology 20211111 11

Covalent conjugation of allergens to toll-like receptor (TLR) agonists appears to be a powerful strategy for the development of safety compounds for allergen-specific immunomodulatory response toward tolerance in allergy. In this work, we have synthesized two family of ligands, an 8-oxoadenine derivative as a ligand for TLR7 and a pyrimido[5,4-<i>b</i>]indole as a ligand for TLR4, both conjugated with a T-cell peptide of Pru p 3 allergen, the lipid transfer protein (LTP) responsible for LTP-depe ...[more]

PMID: 34761908

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Project description:BackgroundThe immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown.ObjectiveTo identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multiethnic cohorts and responses to OIT.MethodsUntargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N = 384), a Costa Rican cohort of children with asthma (N = 1040), and a peanut OIT trial (N = 20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterward). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes.ResultsCompared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q = 2.4 × 10-20) and linoleic acid derivatives (q = 3.8 × 10-5) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q = 4.1 × 10-8), eicosanoids (q = 7.9 × 10-7), and histidine pathways (q = .015). In particular, the bile acid lithocholate (4.97 [1.93, 16.14], p = .0027), the eicosanoid leukotriene B4 (3.21 [1.38, 8.38], p = .01), and the histidine metabolite urocanic acid (22.13 [3.98, 194.67], p = .0015) were higher in SU.ConclusionsWe observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T-cell subsets, suggesting potential mechanisms of tolerance in immunotherapy.

Dataset Information

Immunomodulatory Response of Toll-like Receptor Ligand-Peptide Conjugates in Food Allergy.

Publications

Immunomodulatory Response of Toll-like Receptor Ligand-Peptide Conjugates in Food Allergy.

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