Department of Hematology and Oncological Sciences, L. and A. Seràgnoli, Institute of Hematology, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy.
Blood. 2012 Sep 20;120(12):2365-75. doi: 10.1182/blood-2012-04-422378. Epub 2012 Jul 11.
Over the past decade, extracellular nucleotides (such as ATP and UTP) have emerged as key immunomodulators. This family of molecules, already known for its key metabolic functions, has been the focus of intense investigation that has unambiguously shown its crucial role as mediators of cell-to-cell communication. More recently, in addition to its involvement in inflammation and immunity, purinergic signaling has also been shown to modulate BM-derived stem cells. Extracellular nucleotides promote proliferation, CXCL12-driven migration, and BM engraftment of hematopoietic progenitor and stem cells. In addition, purinergic signaling acts indirectly on hematopoietic progenitor and stem cells by regulating differentiation and release of proinflammatory cytokines in BM-derived human mesenchymal stromal cells, which are part of the hematopoietic stem cell (HSC) niche. HSC research has recently blended into the field of immunology, as new findings highlighted the role played by immunologic signals (such as IFN-α, IFN-γ, or TNF-α) in the regulation of the HSC compartment. In this review, we summarize recent reports unveiling a previously unsuspected ability of HSCs to integrate inflammatory signals released by immune and stromal cells, with particular emphasis on the dual role of extracellular nucleotides as mediators of both immunologic responses and BM stem cell functions.
在过去的十年中，细胞外核苷酸（如 ATP 和 UTP）已成为关键的免疫调节剂。这些分子已经因其关键的代谢功能而闻名，目前已经成为了激烈研究的焦点，明确显示了它们作为细胞间通讯介质的关键作用。最近，除了参与炎症和免疫反应外，嘌呤能信号还被证明可以调节 BM 来源的干细胞。细胞外核苷酸促进造血祖细胞和干细胞的增殖、CXCL12 驱动的迁移和 BM 植入。此外，嘌呤能信号通过调节 BM 来源的人基质细胞中的促炎细胞因子的分化和释放，间接地作用于造血祖细胞和干细胞，这些细胞是造血干细胞（HSC）龛的一部分。HSC 研究最近融入了免疫学领域，因为新的发现强调了免疫信号（如 IFN-α、IFN-γ 或 TNF-α）在调节 HSC 区室中的作用。在这篇综述中，我们总结了最近的报告，揭示了 HSC 整合免疫和基质细胞释放的炎症信号的先前未被怀疑的能力，特别强调了细胞外核苷酸作为免疫反应和 BM 干细胞功能的双重介质的双重作用。
