双歧杆菌通过肠道DC上调Foxp3+T细胞在类风湿关节炎中的作用及机制研究

Gut flora play vital roles in RA's pathophysiology. RA patients' feces have less bifidobacterium. Bifidobacterium administration selectively promotes immunoregulatory responses, suggesting that this microbe may have therapeutic utility in patients with inflammatory disease. We will exam the changes of gut Bifidobacterium in RA patients and CIA mice. Then feeding mice with this bacteria, to observe the prevention and remission of RA and immunoregulatory responses. In vitro experiments is designed to investigate cross talk between multiple pattern-recognition receptors determines the gut DC and subsequent T regulatory cell response to Bifidobacterium. These findings link microbiota, gastrointestinal mucosa immunity, and rheumatoid arthritis.

肠道菌群是类风湿关节炎重要发病机制。研究显示类风湿关节炎患者体外粪便中双歧杆菌数量减少，双歧杆菌能够通过调节肠道免疫状态，减少炎症反应。因此我们推测双歧杆菌有诱导缓解类风湿关节炎的作用。本研究检测CIA小鼠及RA初发患者肠道双歧杆菌变化，探索双歧杆菌对CIA小鼠关节炎的治疗和预防作用，探讨双歧杆菌作用于CIA小鼠肠道及外周免疫的机制，从而阐明该益生菌通过调节肠道各亚群DC数量，上调Foxp3+T细胞，治疗类风湿关节炎。

肠道菌群失衡在类风湿关节炎（rheumatoid arthritis，RA）发病过程中扮演重要作用。本研究描述了类风湿关节炎患者肠道菌群基本特点，主要菌群分布于五个门，厚壁菌门，拟杆菌门，变形菌门，梭杆菌门和放线菌A。比较初发类风湿关节炎、已治疗类风湿关节炎患者及健康人粪便菌群，三类人群的整体菌群结构有各自的特点，患者菌群多样性较高，且双歧杆菌数量较少。类风湿关节炎患者外周血树突状细胞，包括髓样树突状细胞（myeloid dendritic cells，mDC）和浆细胞样DC（plasmacytoid dendritic cells，pDC）所占百分比较正常人下降，且mDC数量与DAS28评分、压痛关节数与淋巴细胞计数负相关，pDC的数量与DAS28评分负相关。本研究为临床诊断和治疗RA 提供新的靶点及理论依据。