School of Medicine, Research Institute of General Surgery, Southeast University, Jinling Hospital, Nanjing, P.R. China.
Research Institute of General Surgery, Jinling Hospital, Nanjing, P.R. China.
Int Rev Immunol. 2022;41(5):552-563. doi: 10.1080/08830185.2021.1962860. Epub 2021 Aug 6.
Spleen tyrosine kinase (Syk) is a cytoplasmic non-receptor protein tyrosine kinase expressed in a variety of cells and play crucial roles in signal transduction. Syk mediates downstream signaling by recruiting to the dually phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) of the transmembrane adaptor molecule or the receptor chain itself. In gut diseases, Syk is observed to be expressed in intestinal epithelial cells, monocytes/macrophages, dendritic cells and mast cells. Activation of Syk in these cells can modulate intestinal mucosal immune response by promoting inflammatory cytokines and chemokines production, thus regulating gut homeostasis. Due to the restriction of specificity and selectivity for the development of Syk inhibitors, only a few such inhibitors are available in gut diseases, including intestinal ischemia/reperfusion damage, infectious disease, inflammatory bowel disease, etc. The promising outcomes of Syk inhibitors from both preclinical and clinical studies have shown to attenuate the progression of gut diseases thereby indicating a great potential in the development of Syk targeted therapy for treatment of gut diseases. This review depicts the characterization of Syk, summarizes the signal pathways of Syk, and discusses its potential targeted therapy for gut diseases.
脾酪氨酸激酶（Syk）是一种在多种细胞中表达的细胞质非受体蛋白酪氨酸激酶，在信号转导中发挥着关键作用。Syk 通过募集双磷酸化免疫受体酪氨酸基激活基序（ITAMs）的跨膜衔接分子或受体链本身，介导下游信号转导。在肠道疾病中，Syk 被观察到在肠上皮细胞、单核细胞/巨噬细胞、树突状细胞和肥大细胞中表达。这些细胞中 Syk 的激活可以通过促进炎症细胞因子和趋化因子的产生来调节肠道黏膜免疫反应，从而调节肠道内稳态。由于 Syk 抑制剂的发展受到特异性和选择性的限制，目前只有少数几种此类抑制剂可用于肠道疾病，包括肠道缺血/再灌注损伤、传染病、炎症性肠病等。来自临床前和临床研究的 Syk 抑制剂的有前景的结果表明，这些抑制剂可以减轻肠道疾病的进展，从而表明在开发针对 Syk 的靶向治疗肠道疾病方面具有巨大的潜力。本综述描述了 Syk 的特征，总结了 Syk 的信号通路，并讨论了其在肠道疾病中的潜在靶向治疗。
