Abstract
It is now well understood that the bone marrow (BM) compartment can sense systemic inflammatory signals and adapt through increased proliferation and lineage skewing. These coordinated and dynamic alterations in responding hematopoietic stem and progenitor cells (HSPCs), as well as in cells of the bone marrow niche, are increasingly viewed as key contributors to the inflammatory response. Growth factors, cytokines, metabolites, microbial products, and other signals can cause dysregulation across the entire hematopoietic hierarchy, leading to lineage-skewing and even long-term functional adaptations in bone marrow progenitor cells. These alterations may play a central role in the chronicity of disease as well as the links between many common chronic disorders. The possible existence of a form of “memory” in bone marrow progenitor cells is thought to contribute to innate immune responses via the generation of trained immunity (also called innate immune memory). These findings highlight how hematopoietic progenitors dynamically adapt to meet the demand for innate immune cells and how this adaptive response may be beneficial or detrimental depending on the context. In this review, we will discuss the role of bone marrow progenitor cells and their microenvironment in shaping the scope and scale of the immune response in health and disease.
Highlights
Academic Editor: AlexanderThe continuous production of blood cells throughout the lifetime of an organism demands a tightly regulated, yet highly adaptable, system
This study identified a novel epithelial growth factor receptor (Egfr) signaling pathway on bone marrow (BM) endothelial cells that operates as an anti-inflammatory “brake” on diabetes-induced hematopoietic stem and progenitor cells (HSPCs) proliferation, myelopoiesis and wound repair [103]
Findings of a distinct bias toward myeloid cell expansion have been made in murine obesity models, exemplified by increased pools of myeloid progenitor populations, such as MPP3s, common myeloid progenitors (CMPs), granulocyte–monocyte progenitors (GMPs) and pre-granulocyte macrophages [49,135,137–139]
Summary
The continuous production of blood cells throughout the lifetime of an organism demands a tightly regulated, yet highly adaptable, system. The balance between self-renewal and differentiation needs to be strictly controlled to ensure the appropriate production of mature blood cells. This precise control makes certain that the flux into each lineage is maintained and that the relative numbers of mature erythroid, myeloid, and lymphoid cells, that vary significantly, are generated. MPPs have a limited self-renewal capability and exhibit a more restricted lineage differentiation potential [1,7] This highly compartmentalized and structured model of hematopoiesis has been challenged by recent evidence, suggesting that HSCs are not a homogenous pool but are instead a heterogenous mix of cells with distinct behaviors, lineage biases and engraftment potential [8–11]. It is appreciated that the hematopoietic system and its ability to integrate a wide variety of signals ensure that it acts as a key determinant of the host response and a major player in the context of chronic disease
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