Institute of Animal Physiology, Department of Veterinary Sciences and ‡Clinic of Small Animal Medicine, Center of Clinical Veterinary Medicine, LMU Munich , Veterinaerstr. 13, D-80539 Munich, Germany.
J Proteome Res. 2013 Dec 6;12(12):5812-9. doi: 10.1021/pr400837f. Epub 2013 Nov 6.
Autoimmune uveitis is characterized by crossing of blood-retinal barrier (BRB) by autoaggressive immune cells. Equine recurrent uveitis (ERU) is a valuable spontaneous model for autoimmune uveitis and analyses of differentially expressed proteins in ERU unraveled changed protein clusters in target tissues and immune system. Healthy eyes are devoid of leukocytes. In ERU, however, leukocytes enter the inner eye and subsequently destroy it. Molecular mechanisms enabling cell migration through BRB still remain elusive. Previously, we detected decreased talin 1 expression in blood-derived granulocytes of ERU cases, linking the innate immune system to ERU. Because changes in leukocyte protein expression pattern may play a role in pathological abnormalities leading to migration ability, we aimed at identifying interactors of talin 1 in leukocytes with immunoprecipitation, followed by LC-MS/MS for candidate identification. This enabled us to identify CD90 (Thy1) as novel interactor of talin 1 besides several other interactors. In blood-derived granulocytes from healthy individuals, CD90 was highly abundant and significantly reduced in ERU, especially in effector cells. Connection between talin 1 and CD90 and their expression differences in inflammation is an interesting novel finding allowing deeper insight into immune response of innate immune system and granulocyte migration ability in this organ-specific autoimmune disease.
自身免疫性葡萄膜炎的特征是自身攻击性免疫细胞穿过血视网膜屏障 (BRB)。马复发性葡萄膜炎 (ERU) 是一种有价值的自发性自身免疫性葡萄膜炎模型，对 ERU 中差异表达蛋白的分析揭示了靶组织和免疫系统中发生变化的蛋白质簇。健康的眼睛不含白细胞。然而，在 ERU 中，白细胞进入眼内并随后破坏它。允许细胞通过 BRB 迁移的分子机制仍然难以捉摸。先前，我们在 ERU 病例的血液衍生粒细胞中检测到桩蛋白 1 的表达降低，将先天免疫系统与 ERU 联系起来。由于白细胞蛋白表达模式的变化可能在导致迁移能力的病理异常中起作用，我们旨在通过免疫沉淀鉴定白细胞中桩蛋白 1 的相互作用蛋白，然后进行 LC-MS/MS 鉴定候选蛋白。这使我们能够鉴定 CD90（Thy1）作为除其他几个相互作用蛋白之外，桩蛋白 1 的新型相互作用蛋白。在来自健康个体的血液衍生粒细胞中，CD90 高度丰富，在 ERU 中，尤其是在效应细胞中，显著减少。桩蛋白 1 和 CD90 之间的联系及其在炎症中的表达差异是一个有趣的新发现，使我们能够更深入地了解先天免疫系统的免疫反应和这种器官特异性自身免疫性疾病中粒细胞的迁移能力。
