基碳化合物受体的激活通过增强IRF4介导的巨细胞M2极化来减轻肠道炎症
Jiajia Li1, Lu Wang1, Mingyuan Wang1
1Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Biochimica et biophysica acta. Molecular basis of disease
|February 19, 2025
概括
亚利碳化合物受体 (AhR) 激动剂FICZ促进抗炎M2巨分化,通过减少肠道炎症,为克罗恩病 (CD) 提供潜在的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
背景情况:
- 克罗恩氏病 (CD) 涉及免疫细胞失调,特别是巨细胞,它们可以采用亲或抗炎表型.
- 基碳化合物受体 (AhR) 影响肠道炎症,但其在结肠炎期间调节巨细胞两极分化中的作用尚不清楚.
研究的目的:
- 在结肠炎的背景下,研究AhR和巨细胞之间的调节机制.
- 为了确定AhR激活是否影响巨细胞偏向于克罗恩病模型中的抗炎M2表型.
主要方法:
- 在活跃的CD患者的结肠组织中评估M2巨细胞的存在.
- 在使用TNBS的小鼠中诱导大肠炎,并给予AhR激动剂FICZ.
- 在体内和体外使用BMDMs评估结肠炎的严重程度和巨细胞分化.
- 量化了M2标志物和IL-10,并通过siRNA敲击评估了IRF4的作用.
主要成果:
- 与对照组相比,活跃的CD患者显示M2巨细胞减少.
- 治疗FICZ保护小鼠免受TNBS诱导的大肠炎,减少症状和增加M2巨细胞和IL-10.
- 在体外,FICZ促进了BMDM中的M2极化,并对IRF4表达进行了上调.
- 在IRF4中,Knockdown损害了FICZ诱导的M2极化.
结论:
- 激活AhR促进M2巨细胞的两极分化,对肠道炎症产生保护作用.
- 这种有益的效果部分是由IRF4上调调节的介导,这表明CD的新治疗途径.
相关概念视频
01:28Inflammatory Response
1.8K
An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
1.8K
01:24T Cell Types and Functions
897
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
897