Autoreactive T cell is one of the leading causes of immunological tolerance defects in the chronic inflammatory lesions of rheumatoid arthritis (RA). There have been several extracellular signals and intracellular pathways reported in regulating this process but largely remain unknown yet. In this study, we explored the roles of intestinal Wnt/β-catenin on disease severity during collagen-induced arthritis model (CIA), an animal model of RA. We first testified the activity pattern Wnt/β-catenin shifted by intragastric administration of LiCl and DKK-1 in the intestine by real-time PCR and WB analysis. The arthritis scores showing the disease severity in the DKK-1 group was significantly ameliorated compared with the control group at the late stage of the disease, while in the LiCl group, the scores were significantly elevated which was consistent with pathology score analysis of H&E staining. Next, ELISA was performed and showed that TNF-α and IL-17 in the LiCl group were significantly higher than that of the control group. IL-10 in the DKK-1 group was significantly higher than that in the LiCl-1 group and control group, P < 0.05. Flow cytometry of spleen T cells differentiation ratio showed that: Th1 from the DKK-1 and LiCl groups and Th17 from the LiCl group was significantly different from that of the blank model group, P < 0.05. Finally, we explored the effects of intestinal Wnt/β-catenin on T cell differentiation regulator ROR-γt and TCF1 and found that both transcription factors were up-regulated in the LiCl group. Together, these data suggested the pro-information role of Wnt/β-catenin pathway from the intestine in the CIA mouse, implying its use as a potential therapeutic target for the treatment of inflammatory diseases such as RA.

自身反应性T细胞是类风湿性关节炎（RA）慢性炎症病变免疫耐受缺陷的主要原因之一。已经报道了几种调节这一过程的细胞外信号和细胞内途径，但很大程度上仍然未知。在这项研究中，我们探讨了肠道 Wnt/β-catenin 在胶原诱导关节炎模型 (CIA)（一种 RA 动物模型）中对疾病严重程度的作用。我们首先通过实时 PCR 和 WB 分析证实了在肠道内灌胃 LiCl 和 DKK-1 所改变的 Wnt/β-catenin 活性模式。关节炎评分显示，在疾病晚期，DKK-1组的疾病严重程度较对照组明显改善，而LiCl组的评分明显升高，这与H&E染色的病理学评分分析一致。接下来进行ELISA，结果显示LiCl组的TNF-α和IL-17显着高于对照组。 DKK-1组IL-10显着高于LiCl-1组和对照组， P < 0.05。流式细胞术检测脾脏T细胞分化比例显示：DKK-1组和LiCl组Th1、LiCl组Th17与空白模型组差异有显着性， P < 0.05。最后，我们探讨了肠道Wnt/β-catenin对T细胞分化调节因子ROR- γt和TCF1的影响，发现这两个转录因子在LiCl组中均上调。 总之，这些数据表明 CIA 小鼠肠道中的 Wnt/β-catenin 通路具有促信息作用，这意味着它可以作为治疗 RA 等炎症性疾病的潜在治疗靶点。