文章：

系统性TLR2激动剂暴露通过细胞自主和细胞非自主机制调控造血干细胞

Systemic TLR2 agonist exposure regulates hematopoietic stem cells via cell-autonomous and cell-non-autonomous mechanisms

原文发布日期：2016-06-17

DOI: 10.1038/bcj.2016.45

类型: Original Article

开放获取: 是

英文摘要：

Toll-like receptor 2 (TLR2) is a member of the TLR family of receptors that play a central role in innate immunity. In addition to regulating effector immune cells, where it recognizes a wide variety of pathogen-associated and nonpathogen-associated endogenous ligands, TLR2 is expressed in hematopoietic stem cells (HSCs). Its role in HSCs, however, is not well understood. Furthermore, augmented TLR2 signaling is associated with myelodysplastic syndrome, an HSC disorder characterized by ineffective hematopoiesis and a high risk of transformation to leukemia, suggesting that aberrant signaling through this receptor may have clinically significant effects on HSCs. Herein, we show that systemic exposure of mice to a TLR2 agonist leads to an expansion of bone marrow and spleen phenotypic HSCs and progenitors, but a loss of HSC self-renewal capacity. Treatment of chimeric animals shows that these effects are largely cell non-autonomous, with a minor contribution from cell-autonomous TLR2 signaling, and are in part mediated by granulocyte colony-stimulating factor and tumor necrosis factor-α. Together, these data suggest that TLR2 ligand exposure influences HSC cycling and function via unique mechanisms from TLR4, and support an important role for TLR2 in the regulation of HSCs.

摘要翻译： 

Toll样受体2（TLR2）是TLR受体家族成员，在先天免疫中发挥核心作用。除在效应免疫细胞中通过识别多种病原体相关和非病原体相关的内源性配体发挥调控作用外，TLR2还在造血干细胞中表达。然而，其在造血干细胞中的作用尚不明确。此外，增强的TLR2信号传导与骨髓增生异常综合征（一种以无效造血和高白血病转化风险为特征的造血干细胞疾病）相关，表明该受体异常信号可能对造血干细胞产生重要临床影响。本研究显示，小鼠全身性暴露于TLR2激动剂会导致骨髓和脾脏表型造血干细胞及祖细胞扩增，但伴随造血干细胞自我更新能力丧失。嵌合动物实验表明这些效应主要呈细胞非自主性，其中细胞自主性TLR2信号仅起次要作用，且部分由粒细胞集落刺激因子和肿瘤坏死因子-α介导。这些数据共同表明TLR2配体暴露通过不同于TLR4的独特机制影响造血干细胞的周期与功能，为TLR2在造血干细胞调控中的重要作用提供了证据支持。

原文链接：

Systemic TLR2 agonist exposure regulates hematopoietic stem cells via cell-autonomous and cell-non-autonomous mechanisms