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J Immunol ; 204(3): 622-631, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-31871020

RESUMEN

Dendritic cells (DCs) can internalize and cross-present exogenous Ags to CD8+ T cells for pathogen or tumor cell elimination. Recently, growing evidences suggest the possible immunoregulatory role of flavonoids through modulating the Ag presentation of DCs. In this study, we report that naringenin, a grapefruit-derived flavonoid, possesses the ability to increase the Ag cross-presentation in both murine DC line DC2.4 as well as bone marrow-derived DCs, and naringenin-induced moderate intracellular oxidative stress that contributed to the disruption of lysosomal membrane enhanced Ag leakage to cytosol and cross-presentation. Moreover, in a murine colon adenocarcinoma model, naringenin induced more CD103+ DCs infiltration into tumor and facilitated the activation of CD8+ T cells and strengthened the performance of therapeutic E7 vaccine against TC-1 murine lung cancer. Our investigations may inspire novel thoughts for vaccine design and open a new field of potential applications of flavonoids as immunomodulators to improve host protection against infection and tumor.


Asunto(s)
Adenocarcinoma/inmunología , Linfocitos T CD8-positivos/inmunología , Vacunas contra el Cáncer/inmunología , Neoplasias del Colon/inmunología , Células Dendríticas/inmunología , Flavanonas/metabolismo , Neoplasias Pulmonares/inmunología , Proteínas E7 de Papillomavirus/inmunología , Animales , Antígenos CD/metabolismo , Línea Celular Tumoral , Citrus paradisi/inmunología , Reactividad Cruzada , Modelos Animales de Enfermedad , Humanos , Cadenas alfa de Integrinas/metabolismo , Activación de Linfocitos , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo
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