先天免疫反應(Innate immune responses)，在人體免疫系統扮演第一線防禦外來病原菌入侵的重要角色，並且調控後天免疫反應(Adaptive immune responses)的啟動及後續發展。人體細胞可利用Toll-like receptors (TLRs)及細胞質的cytosolic RIG-I-like receptors (RLRs)等Pattern-Recognition Receptors (PRRs)去偵測入侵體內的病原菌。TBK1 (Tank-binding kinase 1)，和IKK是IKK kinase家族的同源基因，它們是磷酸激活酶，在於傳遞TLRs及RLRs活化訊息扮演必須要的角色，進而促進Type I interferons (IFNs)分泌。然而，TBK1的重要性已被證明，但是它的活化機制及其調控的訊息傳遞鏈，仍需進一步研究探討。我們實驗室，藉由研究TBK1訊息傳遞鏈，發現一個新的分子，會和TBK1結合，並位於在Endosomal-Lysosomal compartments，因此我們命名為TAPE (TBK1-Associated Protein in the Endosomal-lysosomal compartment)。我初步的研究發現，TAPE會藉由其N端和TBK1有交互作用，此外TAPE可以協同TBK1去活化IFN-，並可以活化NF-B pathway。我的實驗結果也顯示，TAPE會在許多哺乳類動物細胞株裡表現，並且TAPE會細胞內分佈於endosome及lysosome裡。此外，透過表達TAPE，發現TAPE會有抵抗單純性泡疹病毒 (Herpes Simplex Virus，一個DNA 病毒)以及水泡性口炎病毒(VSV，一個RNA virus)的抗病毒效果。基於上述實驗的發現，我們預測TAPE可能是一個新的先天性免疫反應的調控因子，位於Endosomal-Lysosomal compartments，並且可能參與在病毒藉由endocytic pathway被TLRs所辨識的活化路徑。在未來的研究方向，我們更進一步探討TAPE所調控訊息傳遞鏈，並且確定TAPE參與何者TLRs或是PRRs活化路徑。

Innate immunity serves the first line of host defense against pathogen infection and also bridges to adaptive immunity to build up the full spectrum of immune defenses. Toll-like receptors (TLRs) and cytosolic RIG-I-like receptors (RLRs) are responsible for sensing invading pathogens to trigger innate immune responses. TBK1 (Tank-binding kinase 1) and IKK are non-canonical homolog of IB kinase (IKK) shown to play a key role in linking the TLR and RLR signals to type-I interferon (IFN) activation. However, the TBK1-mediated innate immune pathways remain elusive. Here our group report the identification of a novel TBK1-interacting protein, termed TAPE (TBK1-Associated Protein in the Endosomal-lysosomal compartments), which functions as an activator of innate immunity. Previously, through a proteomic analysis, our group found that TAPE was precipitated in an SRC2-TBK1 signaling complex. I further confirmed that TAPE interacted with TBK1 through its N-terminal region in mammalian cells. Using the luciferase reporter assay, the results showed that TAPE was able to activate both the IFN- and NF-B pathways, suggesting a functional role for TAPE in innate immunity. The tissue expression and subcellular localization of TAPE was examined. My results showed that TAPE was expressed in several cell lines from different tissues. Its distribution in the cell was located in the endosomal and lysosomal compartments, whereby pathogen sensors encounter the invading pathogens through the endocytic pathway. Through the plague assay, the results showed that over expression of TAPE led to the anti-viral responses against herpes simplex virus (HSV, a DNA virus) and vesicular-stomatitis virus (VSV, a RNA virus). Taken together, my study has led to the identification of a novel innate immune regulator, which may function in the endocytic pathway. Future directions will attempt to determine the implication of TAPE in the specific pathogen sensor pathway and to explore its functional roles in vivo.

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