J Immunol：天然免疫通路调控研究取得进展

       近期，中国科学院武汉病毒研究所研究员陈新文领导的研究团队在天然免疫通路调控中取得进展，发现了天然免疫信号通路中的重要信号分子MITA的首个剪接变体MRP，相关的研究结果已发表在国际免疫学期刊The Journal of Immunology上。

       MITA是天然免疫信号通路中的一个重要信号分子，在I型干扰素的诱导产生中发挥着重要作用。尤其是在感知RNA病毒、DNA病毒和细菌第二信号分子过程中不可或缺。目前关于MITA在天然免疫信号通路中的作用已经有了大量的报道，但是关于其如何调控的研究还比较少。该课题组在研究过程中发现了一个MITA的剪接变体蛋白MRP，过表达MRP抑制MITA介导的I型干扰素信号通路，即使存在仙台病毒（SeV）和细菌第二信号分子（c-di-GMP）的刺激过表达MRP仍可以剂量依赖的抑制MITA介导的天然免疫通路。后期的研究表明MRP的抑制机制主要是通过和MITA作用从而影响MITA和TBK1的相互作用进而抑制TBK1对IRF3的磷酸化。

       该研究的主要意义是首次鉴定了一种MITA的剪接变体，并且该剪接变体参与调控MITA介导的信号通路。该研究主要为MITA介导的信号通路研究提供了一种新的调控机制。

J Immunol：天然免疫通路调控研究取得进展

The Journal of Immunology         

An Alternative Splicing Isoform of MITA Antagonizes MITA-Mediated Induction of Type I IFNs

Honghe Chen*， Rongjuan Pei*， Wandi Zhu*， Rui Zeng*， Yun Wang*， Yanyi Wang*， Mengji Lu and Xinwen Chen*

Mediator of IFN regulatory transcription factor 3 activation (MITA) is an important adaptor protein to mediate the induction of type I IFNs. In this study， we identified an alternatively spliced isoform of MITA lacking exon 7， termed MITA-related protein (MRP). MRP shares the N-terminal portion aa 1–253 with MITA but possesses a unique 30-aa sequence at the carboxyl terminal part， therefore lacking the conserved domains including TANK-binding kinase 1 (TBK1) and cyclic diguanylate binding domain. MRP is expressed in multiple tissues and distinct cell lines. Overexpression of MRP inhibited MITA-mediated activation of IFN-β promoter by sendai virus infection and cyclic diguanylate treatment but enhanced that in HSV-1 infection. Interestingly， MRP expression was reduced after Sendai virus infection but was upregulated after HSV-1 infection. Overexpression of MRP inhibited MITA-mediated induction of IFN-β via TBK1-IFN regulatory transcription factor 3 by disrupting the MITA-TBK1 interaction. However， NF-κB pathway was still activated by MRP， as MRP retained the ability to interact with inducible inhibitor of NF-κB (iκB) kinase. Thus， MRP acts as a dominant negative regulator of MITA-mediated induction of IFN production.