Saito Keiichi, Mori Shiro, Kodama Tetsuya
Liaison Centre for Innovative Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan.
Department of Oral and Maxillofacial Surgery, Tohoku University Hospital, Sendai, Japan; Laboratory of Biomedical Engineering for Cancer, Department of Biomedical Engineering, Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan.
Immunol Lett. 2021 Sep;237:3-10. doi: 10.1016/j.imlet.2021.06.003. Epub 2021 Jun 24.
Many studies of the autoimmune disease Sjögren's syndrome have been performed using spontaneous mouse models. In the present study, we describe the characteristics of McH/lpr-RA1 mice and propose their use as a novel murine model of autoimmune sialadenitis. The McH/lpr-RA1 mouse is a recombinant congenic strain derived from generation F54 or more of MRL-Fas x (MRL- Fas x C3H- Fas) F1. We show for the first time that this mouse spontaneously develops autoimmune sialadenitis and vasculitis in submandibular gland tissues. Sialadenitis was accompanied by extensive inflammatory cell infiltration and tissue destruction. Immunohistochemical studies revealed that the salivary gland lesions strongly expressed four sialadenitis-related molecules: SSA and SSB (autoantigens of Sjögren's syndrome), gp91phox (an accelerator of reactive oxygen species production) and single strand DNA (a marker of apoptotic cells). In contrast, expression of aquaporin-5 (AQP5), which stimulates salivary secretion was weak or negligible. Statistical correlation analyses indicated that the apoptosis of salivary gland cells provoked by oxidative stress contributed to the severe sialadenitis and reduced expression of AQP5. Our study has demonstrated that McH/lpr-RA1 mice spontaneously develop the pathognomonic features of autoimmune sialadenitis and thus could be used as a new animal model of Sjögren's syndrome.
许多关于自身免疫性疾病干燥综合征的研究都是使用自发小鼠模型进行的。在本研究中，我们描述了McH/lpr-RA1小鼠的特征，并提出将其用作自身免疫性涎腺炎的新型小鼠模型。McH/lpr-RA1小鼠是一种重组近交系，源自MRL-Fas x (MRL-Fas x C3H-Fas) F1的第54代或更高代。我们首次表明，这种小鼠在颌下腺组织中自发发展为自身免疫性涎腺炎和血管炎。涎腺炎伴有广泛的炎性细胞浸润和组织破坏。免疫组织化学研究显示，唾液腺病变强烈表达四种与涎腺炎相关的分子：SSA和SSB（干燥综合征的自身抗原）、gp91phox（活性氧产生的促进剂）和单链DNA（凋亡细胞的标志物）。相比之下，刺激唾液分泌的水通道蛋白5（AQP5）的表达较弱或可忽略不计。统计相关性分析表明，氧化应激引发的唾液腺细胞凋亡导致了严重的涎腺炎和AQP5表达降低。我们的研究表明，McH/lpr-RA1小鼠自发出现自身免疫性涎腺炎的特征性表现，因此可作为干燥综合征的新动物模型。
