The bone marrow at the crossroads of blood and immunity

• Published in: Nature reviews. Immunology Vol. 12; no. 1; pp. 49 - 60
• Main Authors: Mercier, Francois E., Ragu, Christine, Scadden, David T.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2012; Nature Publishing Group
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Blood; Blood cells; Bone marrow; Bone Marrow - immunology; Bone Marrow - metabolism; Bone Marrow Cells - cytology; Bone Marrow Cells - immunology; Cell cycle; Cell Differentiation; Dendritic cells; Differentiation; Gene expression; Genetic aspects; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Hemopoiesis; Humans; Immune system; Immunity; Immunology; Landscape; Ligands; Physiology; Plasma; Population growth; Regulatory sequences; review-article; Stem Cell Niche - immunology; Stem cells; United Kingdom; United States > US; Massachusetts
• ISSN: 1474-1733; 1474-1741; 1474-1741
• DOI: 10.1038/nri3132

Key Points Bone marrow cellular niches are functional compartments that regulate haematopoietic stem cell (HSC) and immune cell behaviour through direct cell contact, growth factors and cytokines, and components of the extracellular matrix. Within the bone marrow, HSCs are regulated by components of the vasculature, the trabecular bone and the surrounding stroma. In addition to its role as a primary lymphoid organ through the support of lymphoid development, the bone marrow can act as a host for naive and memory immune cells, plasma cells, regulatory T cells and myeloid immune cells. The bone marrow is heterogeneous with regard to perfusion, oxygenation and innervation. Together, studies exploring these features allow us to consider new ways in which the bone marrow cellular niches are constituted and regulated. Because the haematopoietic and immune systems need to rapidly respond and adapt to the needs of the organism, their niches should not be viewed as static entities. For example, these niches can respond to particular states of injury and inflammation. A better understanding of the dynamic interactions between HSCs, immune cells and their niches could yield significant therapeutic benefit in contexts such as chemotherapy, radiation injury or invasion of the niche by malignancies. This Review describes the dynamic interactions that occur between haematopoietic stem cells (HSCs), immune cells and their specialized niches in the bone marrow. The authors discuss how the signals provided by the niche help HSCs and immune cells to respond to injury or inflammation in peripheral tissues. Progenitor cells that are the basis for all blood cell production share the bone marrow with more mature elements of the adaptive immune system. Specialized niches within the bone marrow guide and, at times, constrain the development of haematopoietic stem and progenitor cells (HSPCs) and lineage-restricted immune progenitor cells. Specific niche components are organized into distinct domains to create a diversified landscape in which specialized cell differentiation or population expansion programmes proceed. Local cues that reflect the tissue and organismal state affect cellular interactions to alter the production of a range of cell types. Here, we review the organization of regulatory elements in the bone marrow and discuss how these elements provide a dynamic means for the host to modulate stem cell and adaptive immune cell responses to physiological challenges.