Huang Jijun, Liang Wenting, Zhang Ruizhi, Zhao Yuyang, Shi Rong, Chen Xiangming, Zheng Yanling, Li Xiaomin, Liu Donglian, Wang Haoyang, Liu Jiamin, Liao Yue, Zhang Xinqi, Jiang Zhihan, Fu Cheng, Huang Ting, Shan Xiaokang, Wang Wanlin, Bu Jin, Peng Tieli, Shen Erxia
School of Basic Medical Sciences, The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Guangzhou, Guangdong, China.
State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China.
Inflamm Bowel Dis. 2025 Jun 25. doi: 10.1093/ibd/izaf089.
Bob1 plays a critical role in immune system regulation, particularly in the function of B cells. Its deficiency in the context of colitis remains underexplored. This study investigates the effects of Bob1 (Pou2af1) deficiency on colitis, particularly focusing on immune responses and gut microbiota alterations in a murine model.
In this study, we employed Pou2af1 knockout (KO) and wild-type (WT) mice to investigate the role of Bob1 in dextran sodium sulfate (DSS)-induced colitis. Colitis was induced by administering 2.5% DSS in drinking water for 7 days. Mice were monitored daily for weight loss, stool consistency, and rectal bleeding to calculate the disease activity index (DAI). Colon length was measured, and colon tissues were collected for histological analysis using hematoxylin and eosin (H&E) staining. Flow cytometry was performed to assess germinal center responses as well as the proportion of T helper (Th)1 and Th17 cells in the colonic lamina propria. Metagenomic sequencing was conducted on fecal samples to evaluate gut microbiota composition.
Pou2af1-deficient mice exhibited significantly exacerbated colitis compared to WT mice. This was evidenced by greater weight loss, elevated disease activity index, reduced colon length, and more severe pathological changes. Immune analysis revealed an impaired germinal center response, diminished generation of IgA⁺ plasma cells, and decreased Th17 cells in the colonic lamina propria in Pou2af1-deficient mice. Additionally, microbiota analysis indicated dysbiosis in the Pou2af1-deficient group, with a notable decrease in Bacteroides species and an increase in pro-inflammatory microbes.
The findings suggest that Pou2af1 deficiency exacerbates DSS-induced colitis by impairing immune responses, particularly the germinal center reaction, and altering gut microbiota composition. These alterations contribute to increased disease severity, highlighting the importance of Pou2af1 in maintaining intestinal immune homeostasis.
Bob1在免疫系统调节中发挥关键作用，尤其是在B细胞功能方面。在结肠炎背景下其缺乏情况仍未得到充分研究。本研究调查了Bob1（Pou2af1）缺乏对结肠炎的影响，特别关注小鼠模型中的免疫反应和肠道微生物群变化。
在本研究中，我们使用Pou2af1基因敲除（KO）小鼠和野生型（WT）小鼠来研究Bob1在葡聚糖硫酸钠（DSS）诱导的结肠炎中的作用。通过在饮用水中给予2.5% DSS 7天来诱导结肠炎。每天监测小鼠的体重减轻、粪便稠度和直肠出血情况，以计算疾病活动指数（DAI）。测量结肠长度，并收集结肠组织进行苏木精和伊红（H&E）染色的组织学分析。进行流式细胞术以评估生发中心反应以及结肠固有层中辅助性T（Th）1细胞和Th17细胞的比例。对粪便样本进行宏基因组测序以评估肠道微生物群组成。
与WT小鼠相比，Pou2af1基因缺陷小鼠的结肠炎明显加重。这表现为体重减轻更多、疾病活动指数升高、结肠长度缩短以及更严重的病理变化。免疫分析显示，Pou2af1基因缺陷小鼠的生发中心反应受损、IgA⁺浆细胞生成减少以及结肠固有层中的Th17细胞减少。此外，微生物群分析表明Pou2af1基因缺陷组存在生态失调，拟杆菌属物种显著减少，促炎微生物增加。
研究结果表明，Pou2af1缺乏通过损害免疫反应，特别是生发中心反应，并改变肠道微生物群组成，从而加重DSS诱导的结肠炎。这些改变导致疾病严重程度增加，突出了Pou2af1在维持肠道免疫稳态中的重要性。
Zotero 插件