在纤维化中涉及的非典型单细胞和致病原体的鉴定
Takashi Satoh1,2, Katsuhiro Nakagawa1,2, Fuminori Sugihara3
1Laboratory of Host Defense, World Premier Institute Immunology Frontier Research Center, Osaka University, Osaka, 565-0871, Japan.
Nature
|December 22, 2016
概括
分离核含有非典型单细胞 (SatM) 对纤维化发展至关重要. CCAAT/增强剂结合蛋白β (C/EBPβ) 调节了SATM分化,并且阻止了纤维化的进展.
科学领域:
- 免疫学
- 细胞生物学
- 病理学
背景情况:
- 单细胞和巨细胞是参与平衡和疾病的重要免疫细胞.
- 纤维化是一种严重的疾病,
- 单细胞和巨细胞的激活与纤维化有关,但具体的亚型仍未确定.
研究的目的:
- 鉴定纤维化所涉及的特定单细胞和巨子集.
- 阐明CAAT/增强剂结合蛋白β (C/EBPβ) 在纤维化中的作用.
- 确定纤维化相关单细胞的起源和分化途径.
主要方法:
- 一个新的单细胞子集的识别和特征,SatM (Ceacam1+Msr1+Ly6C-F4/80-Mac1+).
- 在野生型和Cebpb缺乏的小鼠中分析SATM的发育和功能.
- 研究SATM血统追踪和祖先的起源.
- 通过采用转移实验对白素诱导的纤维化进行评估.
主要成果:
- 发现了一种新型单细胞亚群,SatM,具有颗粒细胞特征,在纤维化中起着关键作用.
- CCAAT/增强剂结合蛋白β (C/EBPβ) 对于SATM分化至关重要;Cebpb缺乏完全取消了SATM.
- 缺少血液细胞中的C/ EBPβ的嵌合体小鼠中预防了纤维化,但没有炎症.
- 它们来自Ly6C-FcεRI+颗粒细胞/巨细胞的前代,而不是巨细胞/状细胞的前代.
结论:
- SatM 是一个独特的单细胞子集,对纤维化的致病性至关重要.
- C/EBPβ 是一个关键的调节器,允许SATM与其承诺的原始体区分.
- 向SATM或C/EBPβ可能为纤维化提供新的治疗策略.
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