Toll样受体是一类重要的模式识别受体，在天然免疫反应、炎症反应、自身免疫性疾病以及肿瘤发生与转移等过程中起着非常重要的作用。自Toll首次在果蝇中发现以来，对Toll样受体介导信号转导的研究一直是生命科学领域的研究热点。目前已经有数十种针对Toll样受体的化合物正在进行或者已经完成了临床试验，用来治疗感染、肿瘤、过敏性或自身免疫性疾病。因此，对Toll样受体介导的信号转导及其调节机制的研究不仅在理论上深化对感染与炎症引发的相关疾病的认识，同时对研究和开发针对某些疾病的有效疫苗和药物具有指导性意义。我们的初步结果表明，USP25在各类不同的细胞中都参与调控Toll样受体介导的信号转导。本项目将通过生物化学、细胞以及分子生物学等研究手段，同时结合基因敲除小鼠以及相关动物疾病模型，阐明USP25在Toll样受体介导的信号转导中的功能，探索USP25调节这一过程的机制。

Toll-like receptors (TLRs) play critical roles in innate immune responses, autoimmune diseases as well as in tumorigenesis and tumor metastasis. TLR-mediated signaling has attracted increasing attention in the field of biomedical research since the first Toll was identified in Drosophila. There are about two dozens of chemicals or antibodies targeting TLRs that are or have been finished in clinical trials for treatment of infection, cancer, allergic or autoimmune diseases. Therefore, studying TLR-mediated signaling and its regulation not only makes theoretical advancement in infection and inflammation, but also provides targets for drugs or vaccines designed to treat diseases related to infection and inflammation. We have generated mice deficient in USP25, a deubiquitinating enzyme, and our prelimilary data demonstrate that USP25 regulates signaling initiated by various TLRs. In this study, we plan to analyze the role of USP25 in TLR-mediated signaling and the mechanisms by which USP25 is involved in this process.