Dysfunctional Immune Regulation in Autoimmune Hepatitis: From Pathogenesis to Novel Therapies.
Dysfunctional Immune Regulation in Autoimmune Hepatitis: From Pathogenesis to Novel Therapies.
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DOI：
10.3389/fimmu.2021.746436
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发表时间：
2021
影响因子：
7.3
通讯作者：
Longhi MS
中科院分区：
文献类型：
--
作者：
Vuerich M;Wang N;Kalbasi A;Graham JJ;Longhi MS
自身免疫性肝炎（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的组织学特征为特征的慢性炎症性疾病。AIH的治疗管理仍然依赖于皮质类固醇、硫唑嘌呤和其他免疫抑制剂如钙调磷酸酶抑制剂和吗替麦考酚酯的给药。撤销免疫抑制通常导致疾病复发，并且在某些情况下，治疗无效或与严重副作用相关。因此，了解AIH发病机制的基础是至关重要的，以开发更有效的和耐受性良好的药物能够恢复免疫耐受的肝脏自身抗原。AIH中效应细胞和调节细胞之间的不平衡使肝损伤持续和进展。CD39是维持免疫耐受性的关键胞外酶，其表达和调节受损已在来自AIH患者的T细胞和效应Th17细胞中报道。干扰这些改变的免疫调节途径可能会开辟新的治疗途径，除了限制异常的炎症反应，也将重建免疫稳态。在这篇综述中，我们强调了AIH免疫发病机制的最新发现，并讨论了这些发现如何为新的治疗工具的开发提供信息和指导。
Autoimmune hepatitis (AIH) is a chronic inflammatory disorder characterized by hypergammaglobulinemia, presence of serum autoantibodies and histological features of interface hepatitis. AIH therapeutic management still relies on the administration of corticosteroids, azathioprine and other immunosuppressants like calcineurin inhibitors and mycophenolate mofetil. Withdrawal of immunosuppression often results in disease relapse, and, in some cases, therapy is ineffective or associated with serious side effects. Understanding the mechanisms underlying AIH pathogenesis is therefore of paramount importance to develop more effective and well tolerated agents capable of restoring immunotolerance to liver autoantigens. Imbalance between effector and regulatory cells permits liver damage perpetuation and progression in AIH. Impaired expression and regulation of CD39, an ectoenzyme key to immunotolerance maintenance, have been reported in Tregs and effector Th17-cells derived from AIH patients. Interference with these altered immunoregulatory pathways may open new therapeutic avenues that, in addition to limiting aberrant inflammatory responses, would also reconstitute immune homeostasis. In this review, we highlight the most recent findings in AIH immunopathogenesis and discuss how these could inform and direct the development of novel therapeutic tools.
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影响因子：
15.3
作者：
Apostolou, I;von Boehmer, H
通讯作者：
von Boehmer, H
影响因子：
32.4
作者：
Cao, Xuefang;Cai, Sheng F.;Ley, Timothy J.
通讯作者：
Ley, Timothy J.
影响因子：
8.3
作者：
Arvaniti, Pinelopi;Giannoulis, George;Dalekos, George N.
通讯作者：
Dalekos, George N.
DOI：
10.1097/01.mpg.0000235975.75120.38
发表时间：
2006-11-01
影响因子：
2.9
作者：
Cuarterolo, Miriam;Ciocca, Mirta;Alvarez, Fernando
通讯作者：
Alvarez, Fernando
影响因子：
25.7
作者：
Aw, Marion M.;Dhawan, Anil;Mieli-Vergani, Giorgina
通讯作者：
Mieli-Vergani, Giorgina