PDF(Pubmed)
Abstract：
The perception of circulating granulocytes as cells with a predetermined immune response mainly triggered by pathogens is evolving, recognizing their functional heterogeneity and adaptability, particularly within the neutrophil subset. The involvement of these cells in the pathophysiology of autoimmune uveitis has become increasingly clear, yet their exact role remains elusive. We used an equine model for autoimmune-mediated recurrent pan-uveitis to investigate early responses of granulocytes in different inflammatory environments. For this purpose, we performed differential proteomics on granulocytes from healthy and diseased horses stimulated with IL8, LPS, or PMA. Compared to healthy horses, granulocytes from the recurrent uveitis model significantly changed the cellular abundance of 384 proteins, with a considerable number of specific changes for each stimulant. To gain more insight into the functional impact of these stimulant-specific proteome changes in ERU pathogenesis, we used Ingenuity Pathway Analysis for pathway enrichment. This resulted in specific reaction patterns for each stimulant, with IL8 predominantly promoting Class I MHC-mediated antigen processing and presentation, LPS enhancing processes in phospholipid biosynthesis, and PMA, clearly inducing neutrophil degranulation. These findings shed light on the remarkably differentiated responses of neutrophils, offering valuable insights into their functional heterogeneity in a T-cell-driven disease. Raw data are available via ProteomeXchange with identifier PXD013648.
摘要：
循环粒细胞感知为具有预定免疫反应的细胞，主要由病原体触发，认识到它们的功能异质性和适应性，特别是在中性粒细胞亚群内。这些细胞参与自身免疫性葡萄膜炎的病理生理学已经变得越来越清楚,然而，他们的确切作用仍然难以捉摸。我们使用马自身免疫介导的复发性全葡萄膜炎模型来研究粒细胞在不同炎症环境中的早期反应。为此,我们对来自健康和患病马的粒细胞进行了差异蛋白质组学，或PMA。与健康的马相比，复发性葡萄膜炎模型的粒细胞显着改变了384种蛋白质的细胞丰度，每种兴奋剂都有相当多的具体变化。为了更深入地了解这些兴奋剂特异性蛋白质组变化在ERU发病机理中的功能影响，我们使用独创性途径分析进行途径富集。这导致了每种兴奋剂的特定反应模式，IL8主要促进I类MHC介导的抗原加工和呈递，LPS增强磷脂生物合成过程，和PMA,明确诱导中性粒细胞脱颗粒。这些发现揭示了中性粒细胞的显著分化反应，在T细胞驱动的疾病中提供对其功能异质性的有价值的见解。原始数据可通过具有标识符PXD013648的ProteomeXchange获得。
