Institute of Allergy and Immunology, Shenzhen University, Shenzhen, China.
Inflamm Res. 2013 Mar;62(3):291-7. doi: 10.1007/s00011-012-0577-9. Epub 2012 Dec 11.
The pathogenesis of rheumatoid arthritis (RA) is to be further elucidated. The present study aims to investigate the role of oral antigen in the induction of RA-like inflammation in the articular joints of rats.
An RA animal model was developed by gavage-feeding with antigen and aspirin, and lipopolysaccharide intraperitoneal injection. The gut epithelial barrier function was assessed by the absorption of mannitol and lactose. The absorption of the specific antigen was observed by the immune fluorescent method. The frequency of antigen specific CD4+ T cells in the peripheral system was assessed by flow cytometry. The inflammation in the ankle joints was evaluated by light microscopy and immunohistochemistry.
Rats treated with aspirin showed intestinal barrier dysfunction; high contents of the specific antigen were absorbed into the lamina propria. The antigen specific CD4+ T cells were detected in the spleen that could be activated by exposure to the specific antigen as well as the extracts of joint tissue. High levels of proinflammatory cytokines were detected in the sera. Antigen specific immune complexes were localized in the ankle joints. Heavy extravasation was observed in the synovial cavity. The histology showed an inflammatory feature in the ankle joints.
Oral antigen can induce RA-like inflammation in the articular joints under certain environment such as gut epithelial barrier dysfunction.
类风湿关节炎(RA)的发病机制尚需进一步阐明。本研究旨在探讨口服抗原在诱导大鼠关节类似 RA 炎症中的作用。
通过口服抗原和阿司匹林,并腹腔内注射脂多糖,建立 RA 动物模型。通过甘露醇和乳糖的吸收评估肠道上皮屏障功能。通过免疫荧光法观察特定抗原的吸收。通过流式细胞术评估外周系统中抗原特异性 CD4+T 细胞的频率。通过光镜和免疫组化评估踝关节炎症。
阿司匹林治疗的大鼠表现出肠道屏障功能障碍;大量特定抗原被吸收到固有层。在脾脏中检测到抗原特异性 CD4+T 细胞,这些细胞可以通过暴露于特定抗原以及关节组织提取物而被激活。血清中检测到高水平的促炎细胞因子。抗原特异性免疫复合物定位于踝关节。在滑膜腔中观察到大量渗出。组织学显示踝关节有炎症特征。
在肠道上皮屏障功能障碍等特定环境下,口服抗原可诱导关节类似 RA 的炎症。