Abstract
Key Points
- Obesity represents a substantial public health challenge, including an increased burden of infectious diseases—suggesting the involvement of a compromised immune syste
- Haematopoietic stem cells reside in (and are regulated by) a complex, heterogeneous and tightly controlled microenvironment within the bone marrow
- The bone marrow environment undergoes considerable changes during obesity, including adipocyte hyperplasia and a phenotypic shift of adipocytes towards a white adipose profile
- Methods of limiting the progression of obesity and controlling its systemic and bone-marrow-based sequelae, such as exercise, might represent suitable approaches to maintain haematopoiesis and immune function
This Review seeks to explore the interactions between obesity, and haematopoiesis and the immune system through systemic effects and changes to the primary haematopoietic environment—the bone marrow niche. Firstly, the structure and function of the haematopoietic system is described by introducing the haematopoietic stem cell, its development and differentiation. Secondly, the heterogeneous regulatory environment of the bone marrow is discussed, with several key components described in detail. Thirdly, adipocytes and adipose tissue are described in states of both health and obesity. Fourthly, the available information on the effect of obesity on the bone marrow niche, haematopoiesis and immunity is presented. The article concludes with a focus on methods to suppress bone marrow adiposity.
Innate immunity is evolutionarily conserved in many organisms and enables a rapid defence against pathogens introduced through disease or injury.16 Although innate immunity can distinguish between host and foreign elements at the time an immune response is initiated, that response is not specific, and prolonged activation can readily lead to damage to healthy tissues.16 A suitable example is found in the experimental overexpression of one of the haematopoietic growth factors, granulocyte-macrophage colony-stimulating factor (GM-CSF), which leads to increased numbers and activation of macrophages as well as other leukocytes, resulting in massive inflammation and destruction of normal tissues.17 By contrast, adaptive immunity has the advantage of being highly specific in its targets, because of genetic rearrangements within cell-surface immune receptors and immunoglobulin proteins, and can reliably combat a much wider range of infectious agents.18 This specificity is achieved at the cost of rapid action, however, as lymphocytes of the adaptive immune system must first be primed to respond to specific antigens, at least when encountering a novel agent. Subsequent infections with the same antigen are met more quickly and forcefully with each exposure, as a consequence of immune memory.16, 18