NLRC5 Negatively Regulates the NF-kappa B and Type I Interferon Signaling Pathways

作者：Cui Jun; Zhu Liang; Xia Xiaojun; Wang Helen Y; Legras Xavier; Hong Jun; Ji Jiabing; Shen Pingping; Zheng Shu; Chen Zhijian J; Wang Rong Fu^*

来源：Cell, 2010, 141(3): 483-496.

DOI：10.1016/j.cell.2010.03.040

Stringent control of the NF-kappa B 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-kappa B-dependent responses by interacting with IKK alpha and IKK beta 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-kappa B and its responsive genes, TNF-alpha 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-kappa B and type I interferon signaling pathways and suggest an important role for NLRC5 in homeostatic control of innate immunity.

• 出版日期2010-4-30
• 单位浙江大学; 南京大学