Ushio Aya, Arakaki Rieko, Eguchi Hiroshi, Hotta Fumika, Yamada Akiko, Kudo Yasusei, Ishimaru Naozumi
Departmant of Oral Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8504, Japan.
Department of Ophtalmology, Sakai Hospital Kindai University, Osaka 590-0132, Japan.
Int J Mol Sci. 2017 Jun 6;18(6):1209. doi: 10.3390/ijms18061209.
Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by severe inflammation of exocrine glands such as the salivary and lacrimal glands. When it affects the lacrimal glands, many patients experience keratoconjunctivitis due to severely dry eyes. This study investigated the pathological and immunological characteristics of ocular lesions in a mouse model of SS. Corneal epithelial injury and hyperplasia were confirmed pathologically. The number of conjunctival mucin-producing goblet cells was significantly decreased in the SS model mice compared with control mice. Expression levels of transforming growth factor (TGF)-β, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-X-C motif chemokine (CXCL) 12 were significantly higher in the corneal epithelium of the SS model mice than in control mice. Inflammatory lesions were observed in the Harderian, intraorbital, and extraorbital lacrimal glands in the SS model mice, suggesting that the ocular glands were targeted by an autoimmune response. The lacrimal glands of the SS model mice were infiltrated by cluster of differentiation (CD)4⁺ T cells. Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed significantly increased mRNA expression of TNF-α, TGF-β, CXCL9, and lysozyme in the extraorbital lacrimal glands of the SS model mice compared with control mice. These results add to the understanding of the complex pathogenesis of SS and may facilitate development of new therapeutic strategies.
干燥综合征（SS）是一种全身性自身免疫性疾病，其特征是唾液腺和泪腺等外分泌腺发生严重炎症。当它影响泪腺时，许多患者会因眼睛严重干燥而出现角结膜炎。本研究调查了SS小鼠模型中眼部病变的病理和免疫特征。病理证实存在角膜上皮损伤和增生。与对照小鼠相比，SS模型小鼠结膜中产生粘蛋白的杯状细胞数量显著减少。SS模型小鼠角膜上皮中转化生长因子（TGF）-β、白细胞介素（IL）-6、肿瘤坏死因子（TNF）-α和C-X-C基序趋化因子（CXCL）12的表达水平明显高于对照小鼠。在SS模型小鼠的哈氏腺、眶内和眶外泪腺中观察到炎症病变，表明眼腺是自身免疫反应的靶标。SS模型小鼠的泪腺被分化簇（CD）4⁺ T细胞浸润。实时逆转录-聚合酶链反应（RT-PCR）显示，与对照小鼠相比，SS模型小鼠眶外泪腺中TNF-α、TGF-β、CXCL9和溶菌酶的mRNA表达显著增加。这些结果有助于加深对SS复杂发病机制的理解，并可能促进新治疗策略的开发。
