Macrophages: Key regulators of steady-state and demand-adapted hematopoiesis

Hematopoietic stem cell (HSC) function is required for balanced blood production throughout life; it is thus essential to understand the mechanisms regulating this highly dynamic process. Bone marrow-resident macrophages (Mϕs) have recently emerged as an important component of the HSC niche, where they contribute to regulating HSC and progenitor cell (HSPC) mobilization and function. Here we review the role of macrophages (Mϕs) on immune cell production, HSPC pool size, and mobilization at steady state and under inflammatory conditions. Inflammation induces marked changes in hematopoiesis to restrict or promote generation of specific cell lineages, and this often has a negative impact on HSC function. Cytokines and growth factors induced during inflammation influence hematopoiesis by acting directly on HSPCs and/or by modulating niche cell function. We focus particular attention on the opposing effects of two key inflammatory proteins, interferon-γ and granulocyte-colony stimulating factor, in regulating bone marrow-resident macrophages (Mϕs) and HSPCs. Macrophages (Mϕs) are essential for tissue homeostasis, and here we highlight their emerging role as a central regulator of both steady-state and demand-adapted hematopoiesis.