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 language | English (US) |
---|---|
Pages (from-to) | 483-496 |
Number of pages | 14 |
Journal | Cell |
Volume | 141 |
Issue number | 3 |
DOIs | |
State | Published - Apr 2010 |
Keywords
- Cellimmuno
- Molimmuno
- Signaling
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)