Yan Xiaolong, Zhao Xueyan, Zhou Ming, Sun Yuena, Xu Tianjun
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.
National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, Shanghai, China.
Front Immunol. 2022 Mar 3;13:858179. doi: 10.3389/fimmu.2022.858179. eCollection 2022.
Mediator of IRF3 activation (MITA) is a significant signal adaptor in the retinoic acid-inducible gene-I like receptor (RLR) signaling pathway and plays an important role in the innate immune system. As a transcription factor, nuclear factor kappa B (NF-κB) can be available in many signaling pathways including the RLR signaling pathway and relative to biological processes like immune responses. In this study, it is determined that IRF4b and IRF8 can have a negative effect on NF-κB signaling pathway mediated by MITA in fish. Firstly, it is found that IRF4b and IRF8 have an inhibitory function on MITA-mediated NF-κB signaling pathway. It is interesting that IRF4b and IRF8 have similar functions to achieve precise downregulated and the degradation of MITA through the ubiquitin-proteasome pathway. IRF is taken as the core domain of IRF4b or IRF8 for the downregulation to MITA. This study provides data on MITA-mediated NF-κB signaling pathway in teleost fish and provides new insights into the regulatory mechanism in fish immune system.
干扰素调节因子3激活介质（MITA）是维甲酸诱导基因-I样受体（RLR）信号通路中的一个重要信号衔接蛋白，在先天免疫系统中发挥重要作用。作为一种转录因子，核因子κB（NF-κB）可存在于包括RLR信号通路在内的许多信号通路中，并与免疫反应等生物学过程相关。在本研究中，确定了干扰素调节因子4b（IRF4b）和干扰素调节因子8（IRF8）对鱼类中由MITA介导的NF-κB信号通路具有负面影响。首先，发现IRF4b和IRF8对MITA介导的NF-κB信号通路具有抑制作用。有趣的是，IRF4b和IRF8具有相似的功能，可通过泛素-蛋白酶体途径实现对MITA的精确下调和降解。IRF被视为IRF4b或IRF8对MITA进行下调的核心结构域。本研究提供了硬骨鱼中MITA介导的NF-κB信号通路的数据，并为鱼类免疫系统的调节机制提供了新的见解。
