RT info:eu-repo/semantics/article
T1 Endoplasmic reticulum stress sensor IRE1α enhances IL-23 expression by human dendritic cells
A1 Márquez Piñeiro, Saioa
A1 Fernández, José Javier
A1 Terán Cabanillas, Eli
A1 Herrero Sánchez, María del Carmen
A1 Alonso Martín, Sara
A1 Azogil Rivera, Alicia
A1 Montero Domínguez, Olimpio
A1 Iwawaki, Takao
A1 Cubillos Ruiz, Juan R.
A1 Fernández García, María Nieves
A1 Sánchez Crespo, Mariano
K1 Hongos patógenos
K1 Medical microbiology
K1 Inmunología
K1 Glycolysis
K1 Fungal patterns
K1 Lactate
K1 2302 Bioquímica
K1 2302.21 Biología Molecular
AB 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 postulatedthat 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.
PB Frontiers Media
SN 1664-3224
YR 2017
FD 2017
LK https://uvadoc.uva.es/handle/10324/55130
UL https://uvadoc.uva.es/handle/10324/55130
LA eng
NO Frontiers in Immunology, 2017, Vol. 8, Nº. 639, 19 pp.
NO Producción Científica
DS UVaDOC
RD 07-ago-2024