NLRP12 promotes mouse neutrophil differentiation through regulation of non-canonical NF-κB and MAPKERK1/2 signaling

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)147-155
Number of pages9
JournalInternational Journal of Biological Sciences
Volume14
Issue number2
DOIs
StatePublished - Jan 13 2018

Keywords

  • ERK1/2
  • Myeloid progenitors
  • NF-κB
  • NLRP12
  • Neutrophils differentiation

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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  • Cite this

    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