不同的纤维细胞亚型通过TNFR1信号在小鼠脑膜炎中驱动空间定义的脑膜炎
Lida Iliopoulou1, Christos Tzaferis1, Alejandro Prados1,2
1Institute for Bioinnovation, Biomedical Sciences Research Center "Alexander Fleming", Vari, Greece.
Nature communications
|March 29, 2025
概括
研究人员在小鼠中确定了驱动克罗恩病 (CD) 结核炎的特定纤维细胞子集. 这些细胞组织了三级淋巴体器官,促进了颗粒瘤的形成,突出了它们在疾病进展中的作用.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
背景情况:
- 克罗恩病 (Crohn's disease,简称CD) 是一种慢性炎症性肠病,影响终端大肠.
- 由于TNF过度表达,TnfΔΑRE小鼠模型具有自发性脑膜炎的人类CD.
研究的目的:
- 调查肌细胞群在TNF依赖性脑膜炎中的作用.
- 确定特定的纤维细胞子集参与克罗恩氏病的发病.
主要方法:
- 在TnfΔΑRE小鼠中单细胞RNA测序.
- 对三级淋巴体器官 (TLOs),T细胞重编程和巨细胞积累的分析.
- 功能性实验涉及TNFR1操纵纤维细胞子集.
主要成果:
- 以TLO扩张,T细胞重编程和富含巨细胞的颗粒瘤为特征的乳头炎.
- 减少了 telocytes,trophocytes 和 PdgfraloCd81-细胞的丰富性;扩大的淋巴内皮细胞 (LEC) 和纤维细胞网状细胞 (FRC).
- 在所有三种纤维细胞子集中都发现了促炎特征.
- 维卢斯关联的纤维细胞 (telocytes,PdgfraloCd81-) 通过TNF通路激活和TLO组织启动乳房炎.
- 热细胞驱动疾病的进展和下粘膜粒瘤的形成.
结论:
- 纤维细胞子集在TNF依赖性脑膜炎中空间调节炎症.
- 特定的纤维细胞群在克罗恩氏病样性脑膜炎的发病和进展中发挥着关键作用.
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