The Impact of NLRP3 Activation on Hematopoietic Stem Cell Transplantation

NLRP3激活对造血干细胞移植的影响

NLR family pyrin domain-containing 3 (NLRP3) is an intracellular protein that after recognizing a broad spectrum of stressors, such as microbial motifs and endogenous danger signals, promotes the activation and release of the pro-inflammatory cytokines IL-1β and IL-18, thus playing an essential role in the innate immune response. Several blood cell types, including macrophages, dendritic cells, and hematopoietic stem and progenitor cells (HSPCs), express NLRP3, where it has been implicated in various physiological and pathological processes. For example, NLRP3 participates in the development and expansion of HSPCs, and their release from bone marrow into the peripheral blood has been implicated in certain hematological disorders including various types of leukemia.

NLR 家族含 pyrin 结构域 3 (NLRP3) 是一种细胞内蛋白，在识别微生物基序和内源性危险信号等广谱压力源后，促进促炎细胞因子 IL-1β 和 IL-18 的激活和释放，从而在先天免疫反应中发挥重要作用。几种血细胞类型，包括巨噬细胞、树突细胞和造血干细胞和祖细胞 (HSPC)，表达 NLRP3，它与各种生理和病理过程有关。例如，NLRP3 参与 HSPC 的发育和扩增，它们从骨髓释放到外周血中与某些血液疾病包括各种类型的白血病有关。

 
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In addition, accumulating evidence indicates that activation of NLRP3 plays a pivotal role in the development of transplant complications in patients receiving hematopoietic stem cell transplantation (HSCT) including graft versus host disease, severe infections, and transplant-related mortality. The majority of these complications are triggered by the severe tissue damage derived from the conditioning regimens utilized in HSCT which, in turn, activates NLRP3 and, ultimately, promotes the release of proinflammatory cytokines such as IL-1β and IL-18. Here, we summarize the implications of NLRP3 in HSCT with an emphasis on the involvement of this inflammasome component in transplant complications.

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此外，越来越多的证据表明，NLRP3 的激活在接受造血干细胞移植 (HSCT) 的患者的移植并发症的发展中起着关键作用，包括移植物抗宿主病、严重感染和移植相关死亡率。大多数这些并发症是由 HSCT 中使用的预处理方案引起的严重组织损伤引发的，这反过来激活 NLRP3，并最终促进促炎细胞因子的释放，如 IL-1β 和 IL-18。在这里，我们总结了 NLRP3 在 HSCT 中的意义，重点是这种炎症小体成分在移植并发症中的参与。严重感染和移植相关死亡率。大多数这些并发症是由 HSCT 中使用的预处理方案引起的严重组织损伤引发的，这反过来激活 NLRP3，并最终促进促炎细胞因子的释放，如 IL-1β 和 IL-18。在这里，我们总结了 NLRP3 在 HSCT 中的意义，重点是这种炎症小体成分在移植并发症中的参与。严重感染和移植相关死亡率。大多数这些并发症是由 HSCT 中使用的预处理方案引起的严重组织损伤引发的，这反过来激活 NLRP3，并最终促进促炎细胞因子的释放，如 IL-1β 和 IL-18。在这里，我们总结了 NLRP3 在 HSCT 中的意义，重点是这种炎症小体成分在移植并发症中的参与。

来源：MDPI https://www.mdpi.com/1422-0067/22/21/11845