病毒性肝炎，炎症和癌症：自身免疫的一个教训。

StephenW

J Autoimmun. 2018 Dec;95:58-68. doi: 10.1016/j.jaut.2018.10.021. Epub 2018 Oct 26.
Viral hepatitis, inflammation, and cancer: A lesson for autoimmunity.
Piconese S1, Cammarata I2, Barnaba V3.
Author information

1
    Dipartimento di Medicina Interna e Specialità Mediche, Sapienza University of Rome, Italy; Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy.
2
    Dipartimento di Medicina Interna e Specialità Mediche, Sapienza University of Rome, Italy.
3
    Dipartimento di Medicina Interna e Specialità Mediche, Sapienza University of Rome, Italy; Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy; Center for Life Nano Science, Istituto Italiano di Tecnologia, Rome, Italy. Electronic address: [email protected].

Abstract

In the present review, we analyzed the various overlapping and non-mutually exclusive mechanisms that intersect and form complex and highly flexible immunological networks allowing the defense against liver infections and tumors. Liver immunity results from the combination of the skills of systemic and local immune system(s) to sense and recognize pathogen or tumor antigens, to sensitize a wide range of innate and adaptive immune cells, and to clear the "invaders", through the establishment of a transient liver immunopathology state undergoing resolution/control of infections or tumors, and memory development. Then, a special emphasis is placed on discussing about the capacity of the immune system(s) to develop a state of chronic low-level immunopathology adapting through the intervention of simultaneous immunoregulatory mechanisms, when the liver is infected by highly mutable viruses (e.g., hepatitis B or C viruses [HBV or HCV]) capable to escape from the immune recognition. The establishment of chronic inflammation represents an advantage for the species survival, because it guarantees the long-term survival of human hosts despite the virus persistence. However, chronic inflammation, in the long run, can evolve towards severe consequences (decompensated cirrhosis and hepatocellular carcinoma) in some individuals, finding requiring the impelling need of discovering new therapeutic anti-viral and immunostimulatory agents addressed, in combination, to fight especially HBV that, in contrast to HCV, lacks antivirals capable to eradicate the virus. Finally, we discussed the concept proposing that the divergent immunoregulatory mechanisms that develop in persisting infections or tumors, on the one hand, and autoimmunity, on the other hand, are the mirror image of each other, whose understanding is also relevant for preparing novel immunotherapeutic approaches in autoimmune diseases.
KEYWORDS:

HBV; HCV; Immune checkpoints; Tregs; Wnt

PMID:
    30509387
DOI:
    10.1016/j.jaut.2018.10.021

StephenW

J Autoimmun。 2018年12月; 95：58-68。 doi：10.1016 / j.jaut.2018.10.021。 Epub 2018年10月26日。
病毒性肝炎，炎症和癌症：自身免疫的一个教训。
Piconese S1，Cammarata I2，Barnaba V3。
作者信息

1
    意大利罗马Sapienza大学Dipartimento di Medicina InternaeSpecialitàMediche; Istituto Pasteur Italia  -  Fondazione Cenci Bolognetti，罗马，意大利。
2
    Dipartimento di Medicina InternaeSpecialitàMediche，Sapienza University of Rome，Italy。
3
    意大利罗马Sapienza大学Dipartimento di Medicina InternaeSpecialitàMediche; Istituto Pasteur Italia  -  Fondazione Cenci Bolognetti，罗马，意大利;生命纳米科学中心，Istituto Italiano di Tecnologia，罗马，意大利。电子地址：[email protected]。

抽象

在本综述中，我们分析了各种重叠​​和非相互排斥的机制，这些机制交叉并形成复杂且高度灵活的免疫网络，从而可以防御肝脏感染和肿瘤。肝脏免疫力来自全身和局部免疫系统技能的结合，以感知和识别病原体或肿瘤抗原，使各种先天和适应性免疫细胞敏感，并通过建立清除“入侵者”瞬时肝脏免疫病理状态正在经历感染或肿瘤的消退/控制和记忆发展。然后，特别强调讨论当肝脏被高度可变的病毒感染时，免疫系统能够通过同时免疫调节机制的干预来发展慢性低水平免疫病理状态的能力（例如，乙型或丙型肝炎病毒[HBV或HCV]）能够逃脱免疫识别。慢性炎症的建立代表了物种生存的优势，因为它保证了人类宿主的长期存活，尽管病毒持续存在。然而，从长远来看，慢性炎症可能演变为某些个体的严重后果（失代偿性肝硬化和肝细胞癌），发现需要发现新的治疗性抗病毒和免疫刺激剂，以联合起来对抗特别是HBV与HCV相比，缺乏能够根除病毒的抗病毒药物。最后，我们讨论了这样的概念，即一方面在持续感染或肿瘤中发展的不同免疫调节机制和另一方面，自身免疫是彼此的镜像，其理解也与制备新型免疫治疗相关。自身免疫性疾病的方法。
关键词：

HBV; HCV;免疫检查站;调节性T细胞; Wnt信号

结论：
    30509387
DOI：
    10.1016 / j.jaut.2018.10.021