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嗜酸性粒细胞发育中的转录因子及其作为治疗靶点

Transcription Factors in Eosinophil Development and As Therapeutic Targets.

作者信息

Fulkerson Patricia C

机构信息

Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.

出版信息

Front Med (Lausanne). 2017 Jul 24;4:115. doi: 10.3389/fmed.2017.00115. eCollection 2017.

Abstract

Dynamic gene expression is a major regulatory mechanism that directs hematopoietic cell fate and differentiation, including eosinophil lineage commitment and eosinophil differentiation. Though GATA-1 is well established as a critical transcription factor (TF) for eosinophil development, delineating the transcriptional networks that regulate eosinophil development at homeostasis and in inflammatory states is not complete. Yet, recent advances in molecular experimental tools using purified eosinophil developmental stages have led to identifying new regulators of gene expression during eosinophil development. Herein, recent studies that have provided new insight into the mechanisms of gene regulation during eosinophil lineage commitment and eosinophil differentiation are reviewed. A model is described wherein distinct classes of TFs work together collaborative and hierarchical interactions to direct eosinophil development. In addition, the therapeutic potential for targeting TFs to regulate eosinophil production is discussed. Understanding how specific signals direct distinct patterns of gene expression required for the specialized functions of eosinophils will likely lead to new targets for therapeutic intervention.

摘要

动态基因表达是指导造血细胞命运和分化的主要调控机制,包括嗜酸性粒细胞谱系定向和嗜酸性粒细胞分化。尽管GATA-1作为嗜酸性粒细胞发育的关键转录因子已被充分确立,但阐明在稳态和炎症状态下调节嗜酸性粒细胞发育的转录网络仍不完整。然而,利用纯化的嗜酸性粒细胞发育阶段的分子实验工具的最新进展,已导致在嗜酸性粒细胞发育过程中鉴定出新的基因表达调节因子。本文综述了最近的研究,这些研究为嗜酸性粒细胞谱系定向和嗜酸性粒细胞分化过程中的基因调控机制提供了新的见解。描述了一个模型,其中不同类别的转录因子通过协同和分级相互作用共同指导嗜酸性粒细胞发育。此外,还讨论了靶向转录因子以调节嗜酸性粒细胞产生的治疗潜力。了解特定信号如何指导嗜酸性粒细胞特殊功能所需的不同基因表达模式,可能会带来新的治疗干预靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f67f/5522844/674252668b5f/fmed-04-00115-g001.jpg

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