Immunomodulatory Response of Toll-like Receptor Ligand-Peptide Conjugates in Food Allergy.
Jorge Losada MéndezFrancisca PalomaresFrancisca GómezPedro Ramírez-LópezJavier Ramos-SorianoMaria Jose TorresCristobalina MayorgaJavier RojoPublished in: ACS chemical biology (2021)
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.
Keyphrases
- toll like receptor
- inflammatory response
- nuclear factor
- immune response
- end stage renal disease
- dendritic cells
- ejection fraction
- cell proliferation
- chronic kidney disease
- newly diagnosed
- prognostic factors
- peritoneal dialysis
- early stage
- type diabetes
- photodynamic therapy
- allergic rhinitis
- stem cells
- cell therapy
- signaling pathway
- regulatory t cells
- patient reported outcomes
- cell cycle
- bone marrow
- skeletal muscle
- patient reported
- atopic dermatitis
- fatty acid