Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People's Republic of China.
Medical School of Nanjing University, Nanjing, People's Republic of China.
Adv Exp Med Biol. 2021;1290:81-88. doi: 10.1007/978-3-030-55617-4_5.
Interleukin (IL)-22 belongs to the IL-10 cytokine family which performs biological functions by binding to heterodimer receptors comprising a type 1 receptor chain (R1) and a type 2 receptor chain (R2). IL-22 is mainly derived from CD4+ helper T cells, CD8+ cytotoxic T cells, innate lymphocytes, and natural killer T cells. It can activate downstream signaling pathways such as signal transducer and activator of transcription (STAT)1/3/5, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) through these heterodimer receptors. Although IL-22 is produced by immune cells, its specific receptor IL-22R1 is selectively expressed in nonimmune cells, such as hepatocytes, colonic epithelial cells, and pancreatic epithelial cells (Jiang et al. Hepatology 54(3):900-9, 2011; Jiang et al. BMC Cancer 13:59, 2013; Curd et al. Clin Exp Immunol 168(2):192-9, 2012). Immune cells do not respond to IL-22 stimulation directly within tumors, reports from different groups have revealed that IL-22 can indirectly regulate the tumor microenvironment (TME). In the present chapter, we discuss the roles of IL-22 in malignant cells and immunocytes within the TME, meanwhile, the potential roles of IL-22 as a target for drug discovery will be discussed.
白细胞介素 (IL)-22 属于白细胞介素 10 细胞因子家族，通过与包含 1 型受体链 (R1) 和 2 型受体链 (R2) 的异二聚体受体结合来发挥生物学功能。IL-22 主要来源于 CD4+辅助 T 细胞、CD8+细胞毒性 T 细胞、固有淋巴细胞和自然杀伤 T 细胞。它可以通过这些异二聚体受体激活下游信号通路，如信号转导和转录激活因子 (STAT)1/3/5、核因子 kappa-轻链增强子的激活 B 细胞 (NF-κB)、丝裂原活化蛋白激酶 (MAPK) 和磷酸肌醇 3-激酶 (PI3K)-蛋白激酶 B (AKT)-雷帕霉素 (mTOR)。尽管 IL-22 是由免疫细胞产生的，但它的特异性受体 IL-22R1 选择性地表达在非免疫细胞中，如肝细胞、结肠上皮细胞和胰腺上皮细胞 (Jiang 等人，Hepatology 54(3):900-9, 2011; Jiang 等人，BMC Cancer 13:59, 2013; Curd 等人，Clin Exp Immunol 168(2):192-9, 2012)。免疫细胞在肿瘤内不会直接对 IL-22 刺激作出反应，不同研究组的报告表明，IL-22 可以间接调节肿瘤微环境 (TME)。在本章中，我们讨论了 IL-22 在 TME 中的恶性细胞和免疫细胞中的作用，同时，还将讨论 IL-22 作为药物发现靶点的潜在作用。
