Viral triggers for autoimmunity: is the 'glass of molecular mimicry' half full or half empty?
Viral triggers for autoimmunity: is the 'glass of molecular mimicry' half full or half empty?
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DOI：
10.1016/j.jaut.2009.08.001
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发表时间：
2010-02
影响因子：
12.8
通讯作者：
von Herrath MG
中科院分区：
文献类型：
--
作者：
Christen U;Hintermann E;Holdener M;von Herrath MG
在这篇综述中，我们想要考虑自身免疫性疾病发展的一些要求以及如何在动物模型中复制这种疾病。除了遗传易感性外，环境触发因素似乎在许多自身免疫性疾病的病因学中起着核心作用。从理论上讲，宿主与入侵病原体之间的结构相似性或同一性可能导致宿主的免疫系统不仅对病原体作出反应，而且对自身成分作出反应。然而，为了使这种分子模仿过程诱导自身免疫，需要绕过对自身成分保持耐受性或无知的机制。随后，为了促进自身免疫对抗显性自身免疫性疾病，自身侵袭性淋巴细胞的频率和活跃度必须足够大。直觉上，人们会假设对相同结构的容忍度可能比对具有一定程度相似性的结构的容忍度更强。具有高亲和力的自身反应性淋巴细胞更有可能被中央和/或外周耐受机制删除或功能沉默。因此，由于有效的耐受机制，相同结构之间的完美模仿可能无法诱导自身免疫。相比之下，相似但不相同的结构之间不完美的模仿一方面可能会规避耐受性，另一方面导致淋巴细胞的产生只有低到中等的亲和力。在这里，我们研究了使用分子模仿概念作为诱导或加速自身免疫的潜在机制的动物模型。我们专注于1型糖尿病的RIP-LCMV模型和自身免疫性肝炎的新型细胞色素P450 2D6 （CYP2D6）模型，它们使用相同或相似的触发和靶抗原。
In this review we want to consider some of the requirements for autoimmune disease to develop and how this may be reproduced in animal models. Besides a genetic predisposition, environmental triggering factors seem to play a central role in the etiology of many autoimmune diseases. In theory, a structural similarity or identity between the host and an invading pathogen might cause the immune system of the host to react not only to the pathogen but also to self-components. However, in order for such a process of molecular mimicry to induce autoimmunity the mechanisms of maintaining tolerance or ignorance to the self-components need to be circumvented. Subsequently, in order to advance autoimmunity to overt autoimmune disease the frequency and avidity of autoaggressive lymphocytes has to be of sufficient magnitude. Intuitively, one would assume that tolerance might be stronger to identical structures than to structures that just share a certain degree of similarity. Self-reactive lymphocytes with high-avidity are more likely to be deleted or functionally silenced by central and/or peripheral tolerance mechanisms. Thus, perfect mimicry between identical structures might fail in inducing autoimmunity because of efficient tolerance mechanisms. In contrast, imperfect mimicry between similar but not identical structures might on one hand circumvent tolerance but on the other hand result in the generation of lymphocytes with only low- to intermediate avidity. Here we examine animal models that use the concept of molecular mimicry as a potential mechanism for inducing or accelerating autoimmunity. We focus on the RIP-LCMV model for type 1 diabetes and the novel cytochrome P450 2D6 (CYP2D6) model for autoimmune hepatitis, which use either identical or similar triggering and target antigens.
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影响因子：
15.9
作者：
Coon, B;An, LL;von Herrath, MG
通讯作者：
von Herrath, MG
影响因子：
15.9
作者：
Bowen, DG;Zen, M;Bertolino, P
通讯作者：
Bertolino, P
影响因子：
15.3
作者：
Holdener, Martin;Hintermann, Edith;Bayer, Monika;Rhode, Antje;Rodrigo, Evelyn;Hintereder, Gudrun;Johnson, Eric F.;Gonzalez, Frank J.;Pfeilschifter, Josef;Manns, Michael P.;Herrath, Matthias von G.;Christen, Urs
通讯作者：
Christen, Urs
影响因子：
3.6
作者：
Christen, U;von Herrath, MG
通讯作者：
von Herrath, MG
影响因子：
82.9
作者：
Han, BY;Serra, P;Santamaria, P
通讯作者：
Santamaria, P