Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
Cells. 2021 Jun 4;10(6):1386. doi: 10.3390/cells10061386.
All vertebrate blood cells descend from multipotent hematopoietic stem cells (HSCs), whose activity and differentiation depend on a complex and incompletely understood relationship with inflammatory signals. Although homeostatic levels of inflammatory signaling play an intricate role in HSC maintenance, activation, proliferation, and differentiation, acute or chronic exposure to inflammation can have deleterious effects on HSC function and self-renewal capacity, and bias their differentiation program. Increased levels of inflammatory signaling are observed during aging, affecting HSCs either directly or indirectly via the bone marrow niche and contributing to their loss of self-renewal capacity, diminished overall functionality, and myeloid differentiation skewing. These changes can have significant pathological consequences. Here, we provide an overview of the current literature on the complex interplay between HSCs and inflammatory signaling, and how this relationship contributes to age-related phenotypes. Understanding the mechanisms and outcomes of this interaction during different life stages will have significant implications in the modulation and restoration of the hematopoietic system in human disease, recovery from cancer and chemotherapeutic treatments, stem cell transplantation, and aging.
所有脊椎动物的血细胞都来源于多能造血干细胞（HSCs），其活性和分化依赖于与炎症信号的复杂且不完全了解的关系。尽管炎症信号的稳态水平在 HSC 的维持、激活、增殖和分化中起着复杂的作用，但急性或慢性炎症暴露会对 HSC 的功能和自我更新能力产生有害影响，并使它们的分化程序偏向。在衰老过程中观察到炎症信号水平增加，通过骨髓龛直接或间接地影响 HSCs，并导致其自我更新能力丧失、整体功能下降和骨髓分化偏倚。这些变化可能具有重要的病理后果。在这里，我们概述了关于 HSCs 和炎症信号之间复杂相互作用的最新文献，以及这种关系如何导致与年龄相关的表型。了解不同生命阶段这种相互作用的机制和结果将对人类疾病、癌症和化疗治疗的恢复、干细胞移植以及衰老过程中造血系统的调节和恢复具有重要意义。
