The intervention of intestinal Wnt/β-catenin pathway alters inflammation and disease severity of CIA
The intervention of intestinal Wnt/β-catenin pathway alters inflammation and disease severity of CIA
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肠道Wnt/β-连环蛋白通路干预改变CIA炎症反应和疾病严重程度
DOI：
10.1007/s12026-021-09190-8
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发表时间：
2021-05-26
影响因子：
4.4
通讯作者：
Zhao, Dongbao
中科院分区：
文献类型：
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作者：
Tan, Weixing;Qiu, Yang;Zhao, Dongbao
自体反应性T细胞是类风湿性关节炎（RA）慢性炎性病变中免疫耐受缺陷的主要原因之一。已经报道了一些细胞外信号和细胞内通路调节这一过程，但在很大程度上仍然未知。在本研究中，我们探讨了肠道Wnt/ β -连环蛋白在RA动物模型胶原诱导关节炎模型（CIA）中疾病严重程度的作用。我们首先通过实时荧光定量PCR和WB分析证实了肠内灌胃LiCl和DKK-1后Wnt/ β -连环蛋白的活性模式发生了变化。在疾病晚期，DKK-1组显示疾病严重程度的关节炎评分较对照组明显改善，而LiCl组评分明显升高，这与H&E染色病理评分分析一致。接着进行ELISA检测，结果显示LiCl组的tnf - α和IL-17显著高于对照组。DKK-1组IL-10显著高于LiCl-1组和对照组，P < 0.05。脾T细胞分化率流式细胞术显示：DKK-1和LiCl组Th1和LiCl组Th17与空白模型组比较差异显著，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 - γ T和TCF1的影响，发现LiCl组这两个转录因子均上调。综上所述，这些数据提示来自CIA小鼠肠道的Wnt/ β -catenin通路具有促信息作用，暗示其可作为治疗炎性疾病（如RA）的潜在治疗靶点。
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/beta-catenin on disease severity during collagen-induced arthritis model (CIA), an animal model of RA. We first testified the activity pattern Wnt/beta-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-alpha 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/beta-catenin on T cell differentiation regulator ROR-gamma t 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/beta-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.