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Wei Wang, Xiaodan Qin, Liang Lin, Jia Wu, Xiuyuan Sun, Ye Zhao, Yurong Ju, Ziheng Zhao, Liwei Ren, Xuewen Pang, Youfei Guan, Yu Zhang, Prostaglandin E2–Induced AKT Activation Regulates the Life Span of Short-Lived Plasma Cells by Attenuating IRE1α Hyperactivation, The Journal of Immunology, Volume 208, Issue 8, April 2022, Pages 1912–1923, https://doi.org/10.4049/jimmunol.2100466
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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.