Diabetes Center, University of California-San Francisco, San Francisco, CA 94143, USA.
J Immunol. 2010 Apr 15;184(8):4236-46. doi: 10.4049/jimmunol.0902434. Epub 2010 Mar 17.
Sjögren's Syndrome (SS) is a human autoimmune disease characterized by immune-mediated destruction of the lacrimal and salivary glands. In this study, we show that the Aire-deficient mouse represents a new tool to investigate autoimmune dacryoadenitis and keratoconjunctivitis sicca, features of SS. Previous work in the Aire-deficient mouse suggested a role for alpha-fodrin, a ubiquitous Ag, in the disease process. Using an unbiased biochemical approach, however, we have identified a novel lacrimal gland autoantigen, odorant binding protein 1a, targeted by the autoimmune response. This novel autoantigen is expressed in the thymus in an Aire-dependent manner. The results from our study suggest that defects in central tolerance may contribute to SS and provide a new and clinically relevant model to investigate the pathogenic mechanisms in lacrimal gland autoimmunity and associated ocular surface sequelae.
干燥综合征（SS）是一种人类自身免疫性疾病，其特征是泪腺和唾液腺的免疫介导破坏。在这项研究中，我们表明，Aire 缺陷型小鼠代表了一种新的工具，可以研究自身免疫性泪腺炎和干燥性角膜结膜炎，这是 SS 的特征。Aire 缺陷型小鼠中的先前工作表明，一种普遍存在的 Ag，即α-肌动蛋白在疾病过程中起作用。然而，使用一种无偏见的生化方法，我们已经鉴定出一种新的泪腺自身抗原，即气味结合蛋白 1a，它是自身免疫反应的靶标。这种新的自身抗原在胸腺中以 Aire 依赖性的方式表达。我们的研究结果表明，中枢耐受缺陷可能导致 SS，并提供了一种新的、具有临床相关性的模型，用于研究泪腺自身免疫和相关眼表面后遗症的发病机制。
