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Título
Endoplasmic reticulum stress sensor IRE1α enhances IL-23 expression by human dendritic cells
Autor
Año del Documento
2017
Editorial
Frontiers Media
Descripción
Producción Científica
Documento Fuente
Frontiers in Immunology, 2017, Vol. 8, Nº. 639, 19 pp.
Resumo
Human monocyte-derived dendritic cells (DCs) exposed to pathogen-associated molecular patterns (PAMPs) undergo bioenergetic changes that influence the immune response. We found that stimulation with PAMPs enhanced glycolysis in DCs, whereas oxidative phosphorylation remained unaltered. Glucose starvation and the hexokinase inhibitor 2-deoxy-d-glucose (2-DG) modulated cytokine expression in stimulated DCs. Strikingly, IL23A was markedly induced upon 2-DG treatment, but not during glucose deprivation. Since 2-DG can also rapidly inhibit protein N-glycosylation, we postulated
that this compound could induce IL-23 in DCs via activation of the endoplasmic reticulum (ER) stress response. Indeed, stimulation of DCs with PAMPs in the presence of 2-DG robustly activated inositol-requiring protein 1α (IRE1α) signaling and to a lesser extent the PERK arm of the unfolded protein response. Additional ER stressors such as tunicamycin and thapsigargin also promoted IL-23 expression by PAMP-stimulated DCs. Pharmacological, biochemical, and genetic analyses using conditional knockout mice revealed that IL-23 induction in ER stressed DCs stimulated with PAMPs was IRE1α/X-box binding protein 1-dependent upon zymosan stimulation. Interestingly, we further evidenced PERK-mediated and CAAT/enhancer-binding protein β-dependent trans-activation of IL23A upon lipopolysaccharide treatment. Our findings uncover that the ER stress response can potently modulate cytokine expression in PAMP-stimulated human DCs.
Materias (normalizadas)
Hongos patógenos
Medical microbiology
Inmunología
Materias Unesco
2302 Bioquímica
2302.21 Biología Molecular
Palabras Clave
Glycolysis
Fungal patterns
Lactate
ISSN
1664-3224
Revisión por pares
SI
Patrocinador
Plan Nacional de Salud y Farmacia (Proyecto SAF2013-44521-R)
Version del Editor
Propietario de los Derechos
© 2017 Los Autores
Idioma
eng
Tipo de versión
info:eu-repo/semantics/publishedVersion
Derechos
openAccess
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