Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, University Medical Center Freiburg, University of Freiburg, Freiburg, Germany.
Faculty of Biology, University of Freiburg, Freiburg, Germany.
Front Immunol. 2022 Aug 11;13:951937. doi: 10.3389/fimmu.2022.951937. eCollection 2022.
Hematopoiesis is a remarkable system that plays an important role in not only immune cell function, but also in nutrient transport, hemostasis and wound healing among other functions. Under inflammatory conditions, steady-state hematopoiesis switches to emergency myelopoiesis to give rise to the effector cell types necessary to fight the acute insult. Sustained or aberrant exposure to inflammatory signals has detrimental effects on the hematopoietic system, leading to increased proliferation, DNA damage, different forms of cell death (i.e., apoptosis, pyroptosis and necroptosis) and bone marrow microenvironment modifications. Together, all these changes can cause premature loss of hematopoiesis function. Especially in individuals with inherited bone marrow failure syndromes or immune-mediated aplastic anemia, chronic inflammatory signals may thus aggravate cytopenias and accelerate disease progression. However, the understanding of the inflammation roles in bone marrow failure remains limited. In this review, we summarize the different mechanisms found in mouse models regarding to inflammatory bone marrow failure and discuss implications for future research and clinical practice.
造血是一个重要的系统,不仅在免疫细胞功能中发挥作用,而且在营养物质运输、止血和伤口愈合等功能中也发挥作用。在炎症条件下,稳态造血向应急髓样造血转变,产生对抗急性损伤所需的效应细胞类型。持续或异常暴露于炎症信号对造血系统有不利影响,导致增殖增加、DNA 损伤、不同形式的细胞死亡(即细胞凋亡、细胞焦亡和坏死性凋亡)以及骨髓微环境改变。所有这些变化都会导致造血功能过早丧失。特别是在遗传性骨髓衰竭综合征或免疫介导的再生障碍性贫血患者中,慢性炎症信号可能会加重血细胞减少症并加速疾病进展。然而,人们对炎症在骨髓衰竭中的作用的理解仍然有限。在这篇综述中,我们总结了在小鼠模型中发现的关于炎症性骨髓衰竭的不同机制,并讨论了对未来研究和临床实践的意义。