重庆医科大学附属第二医院感染病科,重庆 400010
Received:04 March 2025,
Revised:2025-06-24,
Accepted:07 July 2025,
Published:28 April 2026
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瞿嘉林,雷宇.嘌呤能信号通路在自身免疫性肝炎发病机制中的研究进展[J].重庆医科大学学报,2026,51(04):522-528.
Qu Jialin,Lei Yu.Research advances in the purinergic signaling pathway in the pathogenesis of autoimmune hepatitis[J].Journal of Chongqing Medical University,2026,51(04):522-528.
瞿嘉林,雷宇.嘌呤能信号通路在自身免疫性肝炎发病机制中的研究进展[J].重庆医科大学学报,2026,51(04):522-528. DOI: 10.13406/j.cnki.cyxb.003910.
Qu Jialin,Lei Yu.Research advances in the purinergic signaling pathway in the pathogenesis of autoimmune hepatitis[J].Journal of Chongqing Medical University,2026,51(04):522-528. DOI: 10.13406/j.cnki.cyxb.003910.
自身免疫性肝炎(autoimmune hepatitis,AIH)是一种以高丙种球蛋白血症、血清自身抗体和界面性肝炎组织学表现为特征的慢性炎症性疾病。近年来,研究表明嘌呤能信号通路在自身免疫性肝炎发病机制中发挥着重要作用。胞外核苷三磷酸二磷酸水解酶-1(ectonucleoside triphosphate diphosphohydrolase-1,ENTPDase-1/CD39)和胞外5'-核苷酸酶(Ecto-5'-Nucleotidase,NT5E/CD73)是2种表达于免疫细胞表面的酶,它们通过代谢级联反应将细胞外的三磷酸腺苷转化为具有免疫调节功能的腺苷,从而介导免疫应答调控。同时,从AIH患者中分离的调节性T细胞(regulatory T cells,Tregs)和辅助性T细胞17(T helper cell 17,Th17)显示出CD39和CD73表达异常以及调节功能受损。针对这些失调通路进行靶向调控有望开发出兼具双重疗效的新型治疗策略,既能有效抑制病理性炎症反应,又可同步恢复免疫稳态。本综述旨在系统探讨嘌呤能信号通路在自身免疫性肝炎中的作用机制并分析其转化为治疗干预手段的潜在价值。
Autoimmune hepatitis(AIH) is a chronic inflammatory liver disorder with the histological features of hypergammaglobulinemia,seropositivity for autoantibodies,and interface hepatitis. In recent years,studies have shown that the purinergic signaling pathways plays a critical role in the pathogenesis of AIH. Ectonucleoside triphosphate diphosphohydrolase-1 and ecto-5'-nucleotidase are membrane-anchored ectoenzyme on immune cell surfaces and can catabolize extracellular adenosine triphosphate into immunoregulatory adenosine through a sequential metabolic cascade,thereby mediating the regulation of immune responses. In addition,regulatory T cells and T helper 17 cells isolated from AIH patients showed abnormal expression of CD39 and CD73 and impaired regulatory function. Targeted modulation of these dysregulated pathways may yield novel therapeutic strategies with dual therapeutic effects of effectively suppressing pathological inflammatory responses and simultaneously restoring immune homeostasis. This article systematically reviews the mechanism of action of the purinergic signaling pathway in AIH and its potential as an interventional method.
Mack CL , Adams D , Assis DN , et al . Diagnosis and management of autoimmune hepatitis in adults and children: 2019 practice guidance and guidelines from the American association for the study of liver diseases [J ] . Hepatology , 2020 , 72 ( 2 ): 671 - 722 .
马 雄 , 王绮夏 , 肖 潇 , 等 . 自身免疫性肝炎诊断和治疗指南(2021) [J ] . 临床肝胆病杂志 , 2022 , 38 ( 1 ): 42 - 49 .
Ma X , Wang QX , Xiao X , et al . Guidelines on the diagnosis and management of autoimmune hepatitis(2021) [J ] . J Clin Hepatol , 2022 , 38 ( 1 ): 42 - 49 .
Li XY , Bai X , Tang YQ , et al . Research progress on the P2X7 receptor in liver injury and hepatocellular carcinoma [J ] . Chem Biol Drug Des , 2023 , 101 ( 3 ): 794 - 808 .
Zhang Y , Li X , Wang H . P2X7 receptor variants in HLA-associated autoimmune hepatitis [J ] . J Autoimmun , 2023 , 135 : 103025 .
张克慧 , 李 勇 . 自身免疫性肝炎病因病理机制研究进展 [J ] . 辽宁中医药大学学报 , 2020 , 22 ( 10 ): 180 - 185 .
Zhang KH , Li Y . Etiopathogenesis of autoimmune hepatitis [J ] . J Liaoning Univ Tradit Chin Med , 2020 , 22 ( 10 ): 180 - 185 .
王 聪 , 吴雄健 , 黄才斌 . 自身免疫性肝病的发病机制及诊疗进展 [J ] . 中外医疗 , 2021 , 40 ( 30 ): 194 - 198 .
Wang C , Wu XJ , Huang CB . Pathogenesis,diagnosis and treatment progress of autoimmune liver disease [J ] . China Foreign Med Treat , 2021 , 40 ( 30 ): 194 - 198 .
Thompson RM , Silva LM . CD73-dependent adenosine signaling attenuates neutrophil activation in rheumatoid arthritis [J ] . Nat Immunol , 2022 , 23 : 1124 - 1135 .
Yuksel M , Wang YP , Tai NW , et al . A novel “humanized mouse” model for autoimmune hepatitis and the association of gut microbiota with liver inflammation [J ] . Hepatology , 2015 , 62 ( 5 ): 1536 - 1550 .
Sakaguchi S . Regulatory T cells: key controllers of immunologic self-tolerance [J ] . Cell , 2000 , 101 ( 5 ): 455 - 458 .
Vuerich M , Wang N , Kalbasi A , et al . Dysfunctional immune regulation in autoimmune hepatitis: from pathogenesis to novel therapies [J ] . Front Immunol , 2021 , 12 : 746436 .
Heine P , Braun N , Sévigny J , et al . The C-terminal cysteine-rich region dictates specific catalytic properties in chimeras of the ectonucleotidases NTPDase1 and NTPDase2 [J ] . Eur J Biochem , 2001 , 268 ( 2 ): 364 - 373 .
Antonioli L , Pacher P , Vizi ES , et al . CD39 and CD73 in immunity and inflammation [J ] . Trends Mol Med , 2013 , 19 ( 6 ): 355 - 367 .
Patt Y , Rojas-Hernandez C , Fekrazad HM , et al . Phase II trial of sorafenib in combination with capecitabine in patients with hepatocellular carcinoma: INST 08-20 [J ] . Oncologist , 2017 , 22 ( 10 ): 1158 -e116.
Wang S , Gao SS , Zhou DX , et al . The role of the CD39-CD73-adenosine pathway in liver disease [J ] . J Cell Physiol , 2021 , 236 ( 2 ): 851 - 862 .
Wang P , Jia JD , Zhang D . Purinergic signalling in liver diseases: Pathological functions and therapeutic opportunities [J ] . JHEP Rep , 2020 , 2 ( 6 ): 100165 .
李慧娟 , 叶 亮 , 张方 , 等 . CD39在肿瘤免疫中的研究进展 [J ] . 东南国防医药 , 2018 , 20 ( 1 ): 45 - 49 .
Li HJ , Ye L , Zhang F , et al . Research progress of CD39 in tumor immunity [J ] . Mil Med J Southeast China , 2018 , 20 ( 1 ): 45 - 49 .
Haskó G , Linden J , Cronstein B , et al . Adenosine receptors: therapeutic aspects for inflammatory and immune diseases [J ] . Nat Rev Drug Discov , 2008 , 7 ( 9 ): 759 - 770 .
Junger WG . Immune cell regulation by autocrine purinergic signalling [J ] . Nat Rev Immunol , 2011 , 11 ( 3 ): 201 - 212 .
Allard D , Chrobak P , Allard B , et al . Targeting the CD73-adenosine axis in immuno-oncology [J ] . Immunol Lett , 2019 , 205 : 31 - 39 .
李 明 , 李邻峰 . 调节性T细胞CD39-CD73-腺苷通路在过敏性疾病中的作用 [J ] . 中华临床免疫和变态反应杂志 , 2019 , 13 ( 3 ): 232 - 235 .
Li M , Li LF . Role of CD39-CD73-adenosine pathway of regulatory T cells in allergic diseases [J ] . Chin J Allergy Clin Immunol , 2019 , 13 ( 3 ): 232 - 235 .
路 遥 , 孙芳芳 , 曾 湛 , 等 . 自身免疫性肝炎研究进展 [J/OL ] . 中国肝脏病杂志 (电子版), 2022 , 14 ( 4 ): 1 - 9 .
Lu Y , Sun FF , Zeng Z , et al . Research advances on autoimmune hepatitis [J/OL ] . Chin J Liver Dis Electron Version , 2022 , 14 ( 4 ): 1 - 9 .
郝君玉 , 刘光伟 , 谢 露 , 等 . 中药有效成分干预自身免疫性肝炎相关信号通路的研究进展 [J ] . 临床肝胆病杂志 , 2023 , 39 ( 3 ): 663 - 670 .
Hao JY , Liu GW , Xie L , et al . Research advances in effective constituents of traditional Chinese medicine in intervention of autoimmune hepatitis-related signaling pathways [J ] . J Clin Hepatol , 2023 , 39 ( 3 ): 663 - 670 .
Luz HL , Reichel M , Unwin RJ , et al . P2X7 receptor stimulation is not required for oxalate crystal-induced kidney injury [J ] . Sci Rep , 2019 , 9 ( 1 ): 20086 .
Cuarterolo M , Ciocca M , Velasco CC , et al . Follow-up of children with autoimmune hepatitis treated with cyclosporine [J ] . J Pediatr Gastroenterol Nutr , 2006 , 43 ( 5 ): 635 - 639 .
Wang TQ , Sun GY , Wang YN , et al . The immunoregulatory effects of CD8 T-cell-derived perforin on diet-induced nonalcoholic steatohepatitis [J ] . FASEB J , 2019 , 33 ( 7 ): 8490 - 8503 .
Iracheta-Vellve A , Petrasek J , Satishchandran A , et al . Inhibition of sterile danger signals,uric acid and ATP,prevents inflammasome activation and protects from alcoholic steatohepatitis in mice [J ] . J Hepatol , 2015 , 63 ( 5 ): 1147 - 1155 .
Xia GQ , Cai JN , Wu X , et al . The mechanism by which ATP regulates alcoholic steatohepatitis through P2X4 and CD39 [J ] . Eur J Pharmacol , 2022 , 916 : 174729 .
秦 迁 , 闫 肃 , 杨阳 , 等 . 血尿酸轨迹与代谢相关脂肪性肝病的相关性纵向数据研究 [J ] . 中国预防医学杂志 , 2023 , 24 ( 8 ): 814 - 819 .
Qin Q , Yan S , Yang Y , et al . The correlation between serum uric acid trajectory and metabolic associated fatty liver disease: a longitudinal data study [J ] . Chin Prev Med , 2023 , 24 ( 8 ): 814 - 819 .
Zhang LL , Wei XB , Wang ZM , et al . NF-κB activation enhances STING signaling by altering microtubule-mediated STING trafficking [J ] . Cell Rep , 2023 , 42 ( 3 ): 112185 .
Jang S , Kwon EJ , Lee JJ . Rheumatoid arthritis: pathogenic roles of diverse immune cells [J ] . Int J Mol Sci , 2022 , 23 ( 2 ): 905 .
Kotschenreuther K , Yan SF , Kofler DM . Migration and homeostasis of regulatory T cells in rheumatoid arthritis [J ] . Front Immunol , 2022 , 13 : 947636 .
Meng F , Guo ZG , Hu YL , et al . CD73-derived adenosine controls inflammation and neurodegeneration by modulating dopamine signalling [J ] . Brain , 2019 , 142 ( 3 ): 700 - 718 .
Liberal R , Grant CR , Ma Y , et al . CD39 mediated regulation of Th17-cell effector function is impaired in juvenile autoimmune liver disease [J ] . J Autoimmun , 2016 , 72 : 102 - 112 .
Grant CR , Liberal R , Holder BS , et al . Dysfunctional CD39(POS) regulatory T cells and aberrant control of T-helper type 17 cells in autoimmune hepatitis [J ] . Hepatology , 2014 , 59 ( 3 ): 1007 - 1015 .
Spatola BN , Lerner AG , Wong C , et al . Fully human anti-CD39 antibody potently inhibits ATPase activity in cancer cells via uncompetitive allosteric mechanism [J ] . MAbs , 2020 , 12 ( 1 ): 1838036 .
Vuerich M , Mukherjee S , Robson SC , et al . Control of gut inflammation by modulation of purinergic signaling [J ] . Front Immunol , 2020 , 11 : 1882 .
Wang MR , Li PJ , Li ZW , et al . Lateral septum adenosine A 2A receptors control stress-induced depressive-like behaviors via signaling to the hypothalamus and habenula [J ] . Nat Commun , 2023 , 14 ( 1 ): 1880 .
国际肝胆胰协会中国分会 . Laennec间隙引导肝胆外科手术专家共识(2026版) [J ] . 中华消化外科杂志 , 2026 , 25 ( 1 ): 26 - 34 .
Chinese Chapter of International Hepato-Pancreato-Biliary Association . Expert consensus on Laennec capsule-guided hepatobiliary surgery(2026 edition) [J ] . Chin J Dig Surg , 2026 , 25 ( 1 ): 26 - 34 .
王闪闪 , 张庆山 , 赵素贤 , 等 . 肿瘤坏死因子α诱导蛋白8样分子2在不同肝脏疾病中的免疫调控作用 [J ] . 临床肝胆病杂志 , 2020 , 36 ( 2 ): 460 - 463 .
Wang SS , Zhang QS , Zhao SX , et al . The immunoregulatory effect of tumor necrosis factor-alpha-induced protein 8-like 2 in different liver diseases [J ] . J Clin Hepatol , 2020 , 36 ( 2 ): 460 - 463 .
Gelin CF , Bhattacharya A , Letavic MA . P2X7 receptor antagonists for the treatment of systemic inflammatory disorders [J ] . Prog Med Chem , 2020 , 59 : 63 - 99 .
Allard B , Allard D , Buisseret L , et al . Publisher Correction: The adenosine pathway in immuno-oncology [J ] . Nat Rev Clin Oncol , 2020 , 17 ( 10 ): 650 .
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