Microbial pathways to subvert host immunity generate citrullinated neoantigens targeted in rheumatoid arthritis.

Microbial pathways to subvert host immunity generate citrullinated neoantigens targeted in rheumatoid arthritis.
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DOI:
10.1016/j.sbi.2022.102423
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发表时间:
2022-08
影响因子:
6.8
通讯作者:
Andrade, Felipe
Andrade, Felipe
中科院分区:
生物学2区
文献类型:
--
作者:
Gomez-Banuelos, Eduardo;Konig, Maximilian F.;Andrade, Felipe

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瓜氨酸化蛋白抗体与类风湿性关节炎(RA)之间的特异性相关性使人们对理解瓜氨酸化蛋白在这种疾病中具有免疫原性的原因产生了兴趣,这被认为是RA中自身免疫的起源。由于瓜氨酸是一种生理性翻译后修饰(PTM),因此有一种理论认为,促进瓜氨酸异常的条件是RA中对瓜氨酸化蛋白的自身反应性免疫应答的启动剂。使瓜氨酸正常平衡失调的最主要的候选物是微生物剂,其可以利用瓜氨酸作为效应器机制来破坏宿主的抗微生物活性并使其后代最大化。在这里,我们将使用宿主-病原体界面作为一个统一的模型,将微生物诱导的瓜氨酸酶与RA中瓜氨酸化抗原免疫耐受性的丧失联系起来。
The specific association between antibodies to citrullinated proteins and rheumatoid arthritis (RA) has centered interest on understanding why citrullinated proteins become immunogenic in this disease, which is believed to inform the origins of autoimmunity in RA. Since citrullination is a physiologic post-translational modification (PTM), one theory is that conditions promoting abnormal citrullination are initiators of self-reactive immune responses to citrullinated proteins in RA. Foremost candidates that dysregulate the normal balance of citrullination are microbial agents, which can exploit citrullination as an effector mechanism to subvert host antimicrobial activities and maximize their progeny. Here, we will use the host-pathogen interface as a unifying model to link microbe-induced citrullination and the loss of immunological tolerance to citrullinated antigens in RA.
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