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What Makes Cornea Immunologically Unique and Privileged? Mechanistic Clues from a High-Resolution Proteomic Landscape of the Human Cornea.
OMICS: A Journal of Integrative Biology ( IF 3.3 ) Pub Date : 2020-03-03 , DOI: 10.1089/omi.2019.0190
Yashwanth Subbannayya 1 , Sneha M Pinto 1 , Varshasnata Mohanty 1 , Shobha Dagamajalu 1 , Thottethodi Subrahmanya Keshava Prasad 1 , Krishna R Murthy 2, 3, 4, 5
Affiliation  

Success rates of corneal transplantation are particularly high owing to its unique, innate immune privilege derived from a phenomenon known as Anterior Chamber-Associated Immune Deviation (ACAID). Of note, cornea is a transparent, avascular structure that acts as a barrier along with sclera to protect the eye and contributes to optical power. Molecular and systems biology mechanisms underlying ACAID and the immunologically unique and privileged status of cornea are not well known. We report here a global unbiased proteomic profiling of the human cornea and the identification of 4824 proteins, the largest catalog of human corneal proteins identified to date. Moreover, signaling pathway analysis revealed enrichment of spliceosome, phagosome, lysosome, and focal adhesion pathways, thereby demonstrating the protective functions of corneal proteins. We observed an enrichment of neutrophil-mediated immune response processes in the cornea as well as proteins belonging to the complement and ER-Phagosome pathways that are suggestive of active immune and inflammatory surveillance response. This study provides a key expression map of the corneal proteome repertoire that should enable future translational medicine studies on the pathological conditions of the cornea and the mechanisms by which cornea immunology are governed. Molecular mechanisms of corneal immune privilege have broad relevance to understand and anticipate graft rejection in the field of organ transplantation.

中文翻译:

是什么使角膜在免疫学上具有独特性和特权?来自人类角膜的高分辨率蛋白质组学景观的机械线索。

角膜移植的成功率特别高,这归因于其独特的先天免疫特权,这种特权源自一种称为前房相关免疫偏差(ACAID)的现象。值得注意的是,角膜是透明的无血管结构,与巩膜一起起到屏障的作用,以保护眼睛并有助于提高屈光力。ACAID和角膜的免疫学独特和特权地位的分子和系统生物学机制尚不清楚。我们在这里报告了人类角膜的全球无偏蛋白质组分析和4824蛋白质的鉴定,这是迄今为止确定的人类角膜蛋白质的最大目录。此外,信号通路分析表明,剪接体,吞噬体,溶酶体和粘着斑通路富集,从而证明了角膜蛋白的保护功能。我们观察到角膜中嗜中性粒细胞介导的免疫反应过程以及属于补体和ER-Phagosome途径的蛋白质的富集,提示活跃的免疫和炎症监视反应。这项研究提供了角膜蛋白质组库的关键表达图谱,该图谱应能使未来的转化医学研究角膜的病理状况以及控制角膜免疫学的机制成为可能。角膜免疫特权的分子机制与了解和预期器官移植领域的移植排斥反应有着广泛的联系。
更新日期:2020-03-03
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