...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The journal of clinical investigation >Increased Fanconi C expression contributes to the emergency granulopoiesis response
【24h】

Increased Fanconi C expression contributes to the emergency granulopoiesis response

机译：Fanconi C表达增加有助于紧急粒细胞生成反应

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Emergency granulopoiesis is a component of the innate immune response that is induced in response to infectious or inflammatory challenge. It is characterized by the rapid expansion and differentiation of granulocyte/monocyte progenitor (GMP) populations, which is due in part to a shortened S-phase of the cell cycle. We found that IRF8 (also known as ICSBP), an interferon regulatory transcription factor that activates phagocyte effector genes during the innate immune response, activates the gene encoding Fanconi C ( Fancc ) in murine myeloid progenitor cells. Moreover, IRF8-induced Fancc transcription was augmented by treatment with IL-1β, an essential cytokine for emergency granulopoiesis. The Fanconi pathway participates in repair of stalled or collapsed replication forks during DNA replication, leading us to hypothesize that the Fanconi pathway contributes to genomic stability during emergency granulopoiesis. In support of this hypothesis, Fancc~(–/–) mice developed anemia and neutropenia during repeated, failed episodes of emergency granulopoiesis. Failed emergency granulopoiesis in Fancc~(–/–) mice was associated with excess apoptosis of HSCs and progenitor cells in the bone marrow and impaired HSC function. These studies have implications for understanding the pathogenesis of bone marrow failure in Fanconi anemia and suggest possible therapeutic approaches.
机译：紧急粒细胞生成是先天性免疫反应的组成部分，其是对传染性或炎性挑战的应答。它的特征在于粒细胞/单核细胞祖细胞（GMP）群体的快速扩增和分化，部分原因是细胞周期的S期缩短。我们发现IRF8（也称为ICSBP）是一种干扰素调节转录因子，可在先天免疫应答过程中激活吞噬细胞效应基因，并在鼠骨髓祖细胞中激活编码Fanconi C（Fancc）的基因。此外，通过用IL-1β治疗，IRF8诱导的Fancc转录得以增强，IL-1β是紧急粒细胞生成的必需细胞因子。 Fanconi途径参与DNA复制过程中停滞或折叠的复制叉的修复，这使我们假设Fanconi途径在紧急粒细胞生成过程中有助于基因组稳定性。为支持这一假设，Fancc〜（– / –）小鼠在反复出现的紧急粒细胞生成失败事件中出现了贫血和中性粒细胞减少。 Fancc〜（– / –）小鼠的紧急粒细胞生成失败与骨髓中HSCs和祖细胞的过度凋亡以及HSC功能受损有关。这些研究对于理解范可尼贫血中骨髓衰竭的发病机理具有重要意义，并提出了可能的治疗方法。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号