X-linked inhibitor of apoptosis protein (XIAP)為抑制細胞凋亡家族成員的⼀員，可直接抑制caspase蛋⽩質，並傳遞⾮caspase蛋⽩質路徑訊號。在⾻髓細胞中，XIAP透過其E3泛素連接酶特性參與多個不受caspase蛋⽩質抑制的細胞傳遞訊號路徑。先前實驗室研究已知XIAP參與了T細胞受體（TCR）和IL-6 細胞激素共同活化的訊號傳遞路徑。然⽽在TCR和IL-6 共同活化下, XIAP 詳細作⽤機制仍不明確。在本篇研究中，我們使⽤了XIAP 下調的DO11.10 細胞來探討XIAP 在TCR活化或是IL-6 刺激所扮演的⾓⾊。實驗結果顯⽰XIAP 參與了TCR 活化與TCR 加上IL-6 活化所引起的STAT3 磷酸化。我們也發現，經TCR 活化和TCR 加上IL-6 活化後，MAPK 路徑並不受XIAP 影響。此外，在IL-6 刺激下，XIAP 影響了經TCR活化的mTOR 路徑，但僅經TCR活化的mTOR 路徑則不受XIAP影響。同時，我們也發現到XIAP 下調後發現TGF-β 的RNA表達量增加。這些結果顯⽰XIAP 在JAK-STAT3 路徑中扮演著調節的⾓⾊，並影響下游基因TGF-β 的表現。此外，實驗結果顯⽰XIAP 對STAT3 有著負調節功能，表⽰XIAP 在JAK-STAT3 路徑中可能扮演著關鍵的⾓⾊，並進⼀步調節T細胞功能。

X-linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis protein family that directly inhibits caspases, and transmits caspase-independent signals. XIAP participates in a range of cellular signaling independent of caspase inhibition in myeloid cells via its function in E3 ubiquitin ligase. Previous study of our laboratory showed that XIAP is involved in T cell receptor (TCR) plus IL-6 cytokine activation. However, the involvement detail of XIAP in TCR activation and IL-6 presence remains unclear. In this thesis, we assessed the roles of XIAP in signaling pathways in TCR activation or IL-6 stimulation by XIAP knockdown DO11.10 cells. The results revealed that XIAP participates in STAT3 phosphorylation induced both by TCR- and TCR plus IL-6. We also found that MAPK is affected by XIAP neither in the presence of TCR nor IL-6. Besides, XIAP affects mTOR activation in the presence of IL-6, instead of TCR activation only. It is also found that down regulated XIAP increases TGF-β expression at the RNA level. These findings revealed that XIAP plays role in regulation of JAK-STAT3 pathway, and then affects the expression of downstream gene, TGF-β. Furthermore, the data indicates that XIAP negatively regulates STAT3, suggesting that XIAP may play an essential role in the JAK-STAT3 pathway, and further regulates T cell function.

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