Lorenz Lea, Amann Barbara, Hirmer Sieglinde, Degroote Roxane L, Hauck Stefanie M, Deeg Cornelia A
Chair of Physiology, Department of Veterinary Sciences, LMU Munich, Martinsried 82152, Germany.
Research Unit Protein Science, Helmholtz Center Munich, German Research Center for Environmental Health (GmbH), Munich 80939, Germany.
Glycobiology. 2021 Aug 7;31(7):873-883. doi: 10.1093/glycob/cwab014.
Desialylation of cell surface glycoproteins carried out by sialidases affects various immunological processes. However, the role of neuraminidase 1 (NEU1), one of the four mammalian sialidases, in inflammation and autoimmune disease is not completely unraveled to date. In this study, we analyzed the retinal expression of NEU1 in equine recurrent uveitis (ERU), a spontaneous animal model for autoimmune uveitis. Mass spectrometry revealed significantly higher abundance of NEU1 in retinal Müller glial cells (RMG) of ERU-diseased horses compared to healthy controls. Immunohistochemistry uncovered NEU1 expression along the whole Müller cell body in healthy and uveitic states and confirmed higher abundance in inflamed retina. Müller glial cells are the principal macroglial cells of the retina and play a crucial role in uveitis pathogenesis. To determine whether higher expression levels of NEU1 in uveitic RMG correlate with the desialylation of retinal cells, we performed lectin-binding assays with sialic acid-specific lectins. Through these experiments, we could demonstrate a profound loss of both α2-3- and α2-6-linked terminal sialic acids in uveitis. Hence, we hypothesize that the higher abundance of NEU1 in uveitic RMG plays an important role in the pathogenesis of uveitis by desialylation of retinal cells. As RMG become activated in the course of uveitis and actively promote inflammation, we propose that NEU1 might represent a novel activation marker for inflammatory RMG. Our data provide novel insights in the expression and implication of NEU1 in inflammation and autoimmune disease.
唾液酸酶介导的细胞表面糖蛋白去唾液酸化作用影响多种免疫过程。然而，作为四种哺乳动物唾液酸酶之一的神经氨酸酶1（NEU1）在炎症和自身免疫性疾病中的作用至今尚未完全阐明。在本研究中，我们分析了马复发性葡萄膜炎（ERU）中NEU1在视网膜中的表达情况，ERU是一种自身免疫性葡萄膜炎的自发动物模型。质谱分析显示，与健康对照组相比，患ERU的马的视网膜穆勒神经胶质细胞（RMG）中NEU1的丰度显著更高。免疫组织化学显示，在健康和葡萄膜炎状态下，NEU1沿整个穆勒细胞体表达，并证实其在炎症视网膜中的丰度更高。穆勒神经胶质细胞是视网膜的主要大胶质细胞，在葡萄膜炎发病机制中起关键作用。为了确定葡萄膜炎RMG中NEU1的高表达水平是否与视网膜细胞的去唾液酸化相关，我们用唾液酸特异性凝集素进行了凝集素结合试验。通过这些实验，我们可以证明葡萄膜炎中α2-3-和α2-6-连接的末端唾液酸均有显著丢失。因此，我们推测葡萄膜炎RMG中NEU1的高丰度通过视网膜细胞的去唾液酸化在葡萄膜炎发病机制中起重要作用。由于RMG在葡萄膜炎过程中被激活并积极促进炎症，我们提出NEU1可能是炎症性RMG的一种新型激活标志物。我们的数据为NEU1在炎症和自身免疫性疾病中的表达及意义提供了新的见解。
