NLRP12 Promotes Mouse Neutrophil Differentiation through Regulation of Non-canonical NF-κB and MAPKERK1/2 Signaling

作者：Wang, Qian; Liu, Furao; Zhang, Meichao; Zhou, Pingting; Xu, Ci; Li, Yanyan; Bian, Lei; Liu, Yuanhua; Yao, Yuan; Wang, Fei; Fang, Yong^*; Li, Dong^*

来源：International Journal of Biological Sciences, 2018, 14(2): 147-155.

DOI：10.7150/ijbs.23231

• myeloid progenitors
• NLRP12
• neutrophils differentiation
• NF-kappa B
• ERK1/2

Neutrophils are the most important component of the innate immune system. Mechanistic understanding of the mechanism underlying neutrophil differentiation remains elusive. Using genome-wide RNA-seq, we identified genes whose expression is dramatically up-regulated during neutrophil differentiation. Among them is nucleotide-binding leucine-rich repeat and pyrindomain-containing receptor 12 (NLRP12), which plays a role in immune inflammatory responses. Genetic ablation of NLRP12 suppresses NF-kappa B inducing kinase (NIK) stabilization, RelB nuclear translocation and neutrophil differentiation in vitro. At a mechanistic level, NLRP12 inhibits the activity of mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK1/2), relieves ERK1/2 suppression of NIK protein levels. Thus, NLRP12 enhances noncanonical NF-.B signaling through inhibition of ERK1/2 signaling, thereby promoting neutrophil differentiation.

• 出版日期2018
• 单位江苏省肿瘤防治研究所; 上海交通大学; 南京医科大学