矛盾的是,CCL5通过扭曲巨细胞两极分化来调节淋巴球损伤
Ika N Kadariswantiningsih1,2, Issei Okunaga1, Kaho Yamasaki1
1Department of Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.
JCI insight
|September 23, 2025
概括
在体外,C-C化学因子5 (CCL5) 连接体保护细胞,但在体内会恶化脏疾病. 它在骨髓衍生细胞中的作用驱动着炎症和球损伤,这表明慢性脏病 (CKD) 的向治疗方法.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 慢性病 (CKD) 的进展涉及球体炎症和细胞损失.
- 了解 podocyte-microenvironment 相互作用对于开发有效的CKD 疗法至关重要.
研究的目的:
- 在受伤的 podocytes 中识别炎症媒介.
- 调查C-C化学联体5 (CCL5) 在脏疾病中的悖论性作用.
主要方法:
- 对人类脏活检和CKD小鼠模型的分析.
- 在体外 podocyte 培养和体内 adriamycin 诱导的脏病模型.
- 骨髓移植 (BM) 和小鼠中CCL5缺乏症研究.
主要成果:
- 在受伤的 podocytes 中,CCL5 的水平升高,在体外促进 podocyte 的存活.
- 在体内,CCL5会加剧淋巴细胞损伤,蛋白尿和 podocyte 损失.
- 在BM衍生细胞中的CCL5通过促进M1巨细胞和抑制M2巨细胞驱动疾病的进展.
结论:
- CCL5具有双重效应:体外保护细胞,体内恶化损伤.
- 来自BM细胞的CCL5促进有害的炎症性巨细胞两极分化.
- 在BM衍生细胞中准CCL5可能为缓解CKD中损伤提供治疗策略.
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