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
Citation:
Wang Q, Liu F, Zhang M, Zhou P, Xu C, Li Y, Bian L, Liu Y, Yao Y, Wang F, Fang Y, Li D. NLRP12 Promotes Mouse Neutrophil Differentiation through Regulation of Non-canonical NF-κB and MAPKERK1/2 Signaling. Int J Biol Sci 2018; 14(2):147-155. doi:10.7150/ijbs.23231. https://www.ijbs.com/v14p0147.htm
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.
Wang, Q., Liu, F., Zhang, M., Zhou, P., Xu, C., Li, Y., Bian, L., Liu, Y., Yao, Y., Wang, F., Fang, Y., Li, D. (2018). NLRP12 Promotes Mouse Neutrophil Differentiation through Regulation of Non-canonical NF-κB and MAPKERK1/2 Signaling. International Journal of Biological Sciences, 14(2), 147-155. https://doi.org/10.7150/ijbs.23231.
ACS
Wang, Q.; Liu, F.; Zhang, M.; Zhou, P.; Xu, C.; Li, Y.; Bian, L.; Liu, Y.; Yao, Y.; Wang, F.; Fang, Y.; Li, D. NLRP12 Promotes Mouse Neutrophil Differentiation through Regulation of Non-canonical NF-κB and MAPKERK1/2 Signaling. Int. J. Biol. Sci. 2018, 14 (2), 147-155. DOI: 10.7150/ijbs.23231.
NLM
Wang Q, Liu F, Zhang M, Zhou P, Xu C, Li Y, Bian L, Liu Y, Yao Y, Wang F, Fang Y, Li D. NLRP12 Promotes Mouse Neutrophil Differentiation through Regulation of Non-canonical NF-κB and MAPKERK1/2 Signaling. Int J Biol Sci 2018; 14(2):147-155. doi:10.7150/ijbs.23231. https://www.ijbs.com/v14p0147.htm
CSE
Wang Q, Liu F, Zhang M, Zhou P, Xu C, Li Y, Bian L, Liu Y, Yao Y, Wang F, Fang Y, Li D. 2018. NLRP12 Promotes Mouse Neutrophil Differentiation through Regulation of Non-canonical NF-κB and MAPKERK1/2 Signaling. Int J Biol Sci. 14(2):147-155.
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