Center for Inflammation Research, Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, 02215 Boston, USA.
Center for Inflammation Research, Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, 02215 Boston, USA; Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
Biochem Pharmacol. 2021 May;187:114417. doi: 10.1016/j.bcp.2021.114417. Epub 2021 Jan 15.
CD39 and CD73 control cell immunity by hydrolyzing proinflammatory ATP and ADP (CD39) into AMP, subsequently converted into anti-inflammatory adenosine (CD73). By regulating the balance between effector and regulatory cells, these ectonucleotidases promote immune homeostasis in acute and chronic inflammation; while also appearing to limit antitumor effector immunity in gut cancer. This manuscript focuses on the pivotal role of CD39 and CD73 ectonucleotidase function in shaping immune responses in the gut. We focus on those mechanisms deployed by these critical and pivotal ectoenzymes and the regulation in the setting of gastrointestinal tract infections, inflammatory bowel disease and tumors of the gastrointestinal tract. We will highlight translational and clinical implications of the latest and most innovative basic research discoveries of these important players of the purinergic signaling. Immunotherapeutic strategies that have been developed to either boost or control ectonucleotidase expression and activity in important disease settings are also reviewed and the in vivo effects discussed.
CD39 和 CD73 通过水解促炎的 ATP 和 ADP（CD39）为 AMP，随后将其转化为抗炎的腺苷（CD73）来控制细胞免疫。通过调节效应细胞和调节细胞之间的平衡，这些细胞外核苷酸酶促进急性和慢性炎症中的免疫稳态；同时似乎也限制了胃肠道癌症中的抗肿瘤效应免疫。本文重点关注 CD39 和 CD73 细胞外核苷酸酶在塑造肠道免疫反应中的关键作用。我们专注于这些关键的细胞外酶所采用的机制，以及在胃肠道感染、炎症性肠病和胃肠道肿瘤的背景下的调控。我们将强调这些重要的嘌呤能信号传导分子的最新和最具创新性的基础研究发现的转化和临床意义。本文还回顾了在重要疾病环境中增强或控制细胞外核苷酸酶表达和活性的免疫治疗策略，并讨论了其体内效应。
