增强的骨髓和外骨髓颗粒形成维持了狼性炎的炎症反应
Eleni Zervopoulou1,2, Maria Grigoriou3,4, Stavros A Doumas1,2
1Autoimmunity and Inflammation Laboratory, Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation Academy of Athens, Athens, Greece.
外骨质造血 (EMH) 和训练免疫 (TI) 驱动全身性红斑狼 (SLE),通过促进造血干细胞和原生细胞 (HSPC) 的炎症反应,促进组织损伤和狼性炎 (LN).
科学领域:
- 免疫学 免疫学 免疫学
- 血液学 血液学 血液学
- 类风湿病学 类风湿病学
背景情况:
- 系统性红斑狼 (SLE) 涉及失调的造血,其特征是造血干细胞和原生细胞 (HSPC) 的炎症原始化和骨髓性倾斜.
- 外骨膜造血 (EMH) 涉及到系统性自身免疫性疾病中的组织损伤.
研究的目的:
- 为了研究外骨髓造血 (EMH) 在系统性自身免疫性疾病中的组织损伤中的作用.
- 探索训练免疫 (TI) 对SLE和狼性炎 (LN) 病变发生的贡献.
主要方法:
- 来自SLE患者和易患狼的小鼠的骨髓 (BM) 衍生HSPC的转录和DNA甲基化概况.
- 在狼小鼠模型中使用β-葡萄糖诱导训练免疫 (TI).
- 通过狼性炎 (LN) 组织学分类,殖民地形成单元测定和采用细胞转移来评估疾病活性.
主要成果:
- 骨HSPCs在SLE中比BM对应物具有更高的炎症潜力.
- TI诱导会加剧脏EMH,骨髓曲,并恶化LN.
- 表观遗传变化有助于BM衍生HSPCs的髓状曲;人类SLE发现反映了小鼠模型.
结论:
- 在骨髓和外骨髓部位的原始化HSPCs中衍生出的粒细胞在LN病变发生过程中起着至关重要的作用.
- 通过维持全身炎症和增加疾病爆发风险,EMH和TI有助于SLE.
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