鉴定一种调节人类CD4+T细胞中抗TNF介导IL10表达的转录因子网络
Giovanni A M Povoleri1, Michael L Ridley1, Rebecca J Marrow1
1Centre for Inflammation Biology and Cancer Immunology (CIBCI), Department of Inflammation Biology, School of Immunology & Microbial Sciences, King's College London, London, UK.
Discovery immunology
|September 18, 2024
概括
阻断CD4+T细胞中的瘤亡因子 (TNF) 增强抗炎IL-10. 这项研究确定了参与TNF阻断的MAF,PRDM1和EOMES等关键转录因子.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 炎症研究 炎症研究
背景情况:
- CD4+ T 细胞是免疫媒介性炎症性疾病 (IMID) 的核心.
- 抗瘤坏死因子 (TNF) 治疗对IMIDs有效.
- 之前的研究表明,抗TNF在CD4+T细胞中促进IL-10.
研究的目的:
- 研究通过TNF阻断在CD4+T细胞中诱导IL-10的转录机制.
- 在抗TNF治疗后识别调节IL-10表达的转录因子.
主要方法:
- 来自PBMCs的人类CD4+T细胞被培养成抗CD3/CD28和抗TNF.
- 在CD45RA+细胞枯竭后,进行基因表达概况和染色质可访问性分析.
- 转录因子动机分析确定了IL10位点的候选调节者.
主要成果:
- 抗TNF治疗诱导了CD4+T细胞中独特的基因特征,IL10是最上调的基因.
- 促炎性细胞因子IFNG,IL9,IL22和CXCL10的下调显著.
- 确定了七个候选转录因子,其中MAF,PRDM1和EOMES被建议调节IL10表达.
结论:
- TNF阻断调节CD4+T细胞的转录程序,以促进IL-10的产生.
- 特定的转录因子,包括MAF,PRDM1和EOMES,都与抗TNF介导的IL-10调节有关.
- 这些发现提供了对抗TNF治疗对IMIDs中CD4+T细胞的影响的机制性见解.
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