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

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Leucine
leucine
neutrophils
Neutrophils
Nucleotides
nucleotides
receptors
mice
mitogen-activated protein kinase
protein
immune system
immune response
Proto-Oncogene Proteins c-akt
ablation
translocation
Mitogen-Activated Protein Kinase 1
gene expression
RNA
stabilization
Mitogen-Activated Protein Kinases

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

Cite this

NLRP12 promotes mouse neutrophil differentiation through regulation of non-canonical NF-κB and MAPKERK1/2 signaling. / Wang, Qian; Liu, Furao; Zhang, Meichao; Zhou, Pingting; Xu, Ci; Li, Yanyan; Bian, Lei; Liu, Yuanhua; Yao, Yuan; Wang, Fei; Fang, Yong; Li, Dong.

In: International Journal of Biological Sciences, Vol. 14, No. 2, 13.01.2018, p. 147-155.

Research output: Contribution to journalArticle

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, vol. 14, no. 2, pp. 147-155. https://doi.org/10.7150/ijbs.23231
Wang, Qian ; Liu, Furao ; Zhang, Meichao ; Zhou, Pingting ; Xu, Ci ; Li, Yanyan ; Bian, Lei ; Liu, Yuanhua ; Yao, Yuan ; Wang, Fei ; Fang, Yong ; Li, Dong. / NLRP12 promotes mouse neutrophil differentiation through regulation of non-canonical NF-κB and MAPKERK1/2 signaling. In: International Journal of Biological Sciences. 2018 ; Vol. 14, No. 2. pp. 147-155.
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AU - Bian, Lei

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AB - 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.

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