Prostaglandin E2-Induced AKT Activation Regulates the Life Span of Short-Lived Plasma Cells by Attenuating IRE1α Hyperactivation.
J Immunol
; 208(8): 1912-1923, 2022 04 15.
Article
em En
| MEDLINE
| ID: mdl-35379745
ABSTRACT
The mechanism regulating the life span of short-lived plasma cells (SLPCs) remains poorly understood. Here we demonstrated that the EP4-mediated activation of AKT by PGE2 was required for the proper control of inositol-requiring transmembrane kinase endoribonuclease-1α (IRE1α) hyperactivation and hence the endoplasmic reticulum (ER) homeostasis in IgM-producing SLPCs. Disruption of the PGE2-EP4-AKT signaling pathway resulted in IRE1α-induced activation of JNK, leading to accelerated death of SLPCs. Consequently, Ptger4-deficient mice (C57BL/6) exhibited a markedly impaired IgM response to T-independent Ags and increased susceptibility to Streptococcus pneumoniae infection. This study reveals a highly selective impact of the PGE2-EP4 signal on the humoral immunity and provides a link between ER stress response and the life span of SLPCs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasmócitos
/
Dinoprostona
/
Sobrevivência Celular
/
Proteínas Serina-Treonina Quinases
/
Endorribonucleases
/
Estresse do Retículo Endoplasmático
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China