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Int J Biol Sci 2018; 14(2):147-155. doi:10.7150/ijbs.23231 This issue Cite

Research Paper

NLRP12 Promotes Mouse Neutrophil Differentiation through Regulation of Non-canonical NF-κB and MAPK^ERK1/2 Signaling

Qian Wang^1*, Furao Liu^1*, Meichao Zhang ¹, Pingting Zhou¹, Ci Xu¹, Yanyan Li¹, Lei Bian¹, Yuanhua Liu², Yuan Yao³, Fei Wang⁴, Yong Fang^5✉, Dong Li^1✉

1. Department of Oncology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China;
2. Department of Chemotherapy, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, China;
3. Department of Radiation Oncology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
4. Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
5. Department of Burns and Plastic Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
*These authors have contributed equally to this work

✉ Corresponding authors: Dong Li, Department of Oncology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; E-mail: lidongedu.cn. and Yong Fang, Department of Burns and Plastic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; E-mail: fangyong1020com. More

Abstract

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-κB 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-κB signaling through inhibition of ERK1/2 signaling, thereby promoting neutrophil differentiation.

Keywords: myeloid progenitors, NLRP12, neutrophils differentiation, NF-κB, ERK1/2

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