人类红系分化相关基因对慢性炎症诱导的造血干细胞损伤的保护作用

EDAG protects hematopoietic stem cells from damage induced by chronic inflammation

目的 探究红系分化相关基因(EDAG)在慢性炎症感染下对造血干/祖细胞(HSPC)的影响。方法 将8周龄EDAG^(-/-)小鼠与野生型小鼠分为实验组和对照组,腹腔多次注射单核细胞增生李斯特菌(LM)构建感染性慢性炎症模型,腹腔多次注射低剂量聚胞苷酸[Poly(I∶C)]构建无菌性慢性炎症模型,检测在2种慢性炎症刺激下,EDAG敲除对小鼠造血系统的影响。结果 在LM反复感染模型下,EDAG^(-/-)小鼠出现造血干/祖细胞以及长期造血干细胞(LT-HSC)减少,且外周血出现明显的髓系分化偏向。与此相似,EDAG^(-/-)也可导致无菌性慢性炎症模型中HSPC数量减少,体外集落形成能力下降。结论 在慢性炎症刺激下,EDAG缺失加速年轻小鼠HSPC的耗竭,提示EDAG对慢性炎症诱导的造血干祖细胞损伤具有重要保护作用。

Objective To investigate the effect of erythroid differentiation associated gene(EDAG)on hematopoietic stem/progenitor cells(HSPCs)under chronic inflammation.Methods In this study,EDAG~(-/-)and wild type(WT)mice were divided into the experiment group and control group.An infectious chronic inflammation model was established via multiple intraperitoneal injections of Listeria monocytogenes(LM),while a sterile chronic inflammation model was generated via multiple intraperitoneal injections of polyinosinic-polycytidylic acid[Poly(I∶C)].The effect of EDAG on HSPCs was explored under chronic inflammation conditions.Results In the LM repeated infection model,EDAG deletion led to a decrease in HSPCs and long-term hematopoietic stem cells(LT-HSCs)in mice as well as a significant bias towards myeloid differentiation in peripheral blood.Similarly,EDAG knockout also resulted in reduced numbers of HSPCs and decreased colony-forming ability in aseptic chronic inflammation models.Conclusion EDAG deficiency accelerates HSPC depletion in young mice under chronic inflammation,indicating strong protection of EDAG against HSPC damage induced by chronic inflammation.