Department of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People's Republic of China.
Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS center for Excellence in Molecular Cell Sciences, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, People's Republic of China.
Eur J Immunol. 2018 Nov;48(11):1817-1825. doi: 10.1002/eji.201847589. Epub 2018 Sep 6.
Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are intracellular pattern recognition receptors (PRRs) that regulate a variety of inflammatory and host defense responses. Unlike the well-established NLRs, the roles of NLRP2 are controversial and poorly defined. Here, we report that NLRP2 acts as a negative regulator of TANK-binding kinase 1 (TBK1)-mediated type I interferon (IFN) signaling. Mechanistically, NLRP2 interacted directly with TBK1, and this binding disrupted the interaction of TBK1 and interferon regulatory factor 3 (IRF3), which interfered with TBK1-induced IRF3 phosphorylation. IFNs induce a series of proteins that have well-known antiviral or immune-regulatory functions, and tight control of the IFN signaling cascade is critical for limiting tissue damage and preventing autoimmunity. Our studies indicate that the NLRP2-TBK1 axis may serve as an additional signaling cascade to maintain immune homeostasis in response to viral infection.
核苷酸结合寡聚化结构域（NOD）样受体（NLRs）是细胞内模式识别受体（PRRs），可调节多种炎症和宿主防御反应。与已确立的 NLRs 不同，NLRP2 的作用存在争议且定义不明确。在这里，我们报告 NLRP2 作为 TANK 结合激酶 1（TBK1）介导的 I 型干扰素（IFN）信号的负调节剂。从机制上讲，NLRP2 与 TBK1 直接相互作用，这种结合破坏了 TBK1 和干扰素调节因子 3（IRF3）的相互作用，从而干扰了 TBK1 诱导的 IRF3 磷酸化。IFNs 诱导具有众所周知的抗病毒或免疫调节功能的一系列蛋白质，对 IFN 信号级联的严格控制对于限制组织损伤和预防自身免疫至关重要。我们的研究表明，NLRP2-TBK1 轴可能作为另一个信号级联反应，以响应病毒感染来维持免疫稳态。
