NLRC5 Negatively regulates the NF-κB and type I interferon signaling pathways

Jun Cui, Liang Zhu, Xiaojun Xia, Helen Y. Wang, Xavier Legras, Jun Hong, Jiabing Ji, Pingping Shen, Shu Zheng, Zhijian J. Chen, Rong Fu Wang

Research output: Contribution to journalArticlepeer-review

268 Scopus citations

Abstract

Stringent control of the NF-κB and type I interferon signaling pathways is critical to effective host immune responses, yet the molecular mechanisms that negatively regulate these pathways are poorly understood. Here, we show that NLRC5, a member of the highly conserved NOD-like protein family, can inhibit the IKK complex and RIG-I/MDA5 function. NLRC5 inhibited NF-κB-dependent responses by interacting with IKKα and IKKβ and blocking their phosphorylation. It also interacted with RIG-I and MDA5, but not with MAVS, to inhibit RLR-mediated type I interferon responses. Consistent with these observations, NLRC5-specific siRNA knockdown not only enhanced the activation of NF-κB and its responsive genes, TNF-α and IL-6, but also promoted type I interferon signaling and antiviral immunity. Our findings identify NLRC5 as a negative regulator that blocks two central components of the NF-κB and type I interferon signaling pathways and suggest an important role for NLRC5 in homeostatic control of innate immunity.

Original languageEnglish (US)
Pages (from-to)483-496
Number of pages14
JournalCell
Volume141
Issue number3
DOIs
StatePublished - Apr 2010

Keywords

  • Cellimmuno
  • Molimmuno
  • Signaling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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