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

Abstract

Hematopoietic stem cell (HSC) function is required for balanced blood production throughout life, thus it is 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 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 hematopoietic stem cell (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 gamma (IFNγ) and granulocyte-colony stimulating factor (G-CSF), in regulating bone marrow-resident Mϕs and HSPCs. 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.

Osteomacs interact with megakaryocytes and osteoblasts to regulate murine hematopoietic stem cell function

“…(Figure 2). Based on fluorescence minus one data (supplemental Figure 2), BM-derived macrophages and NCCs are Mac2 low (Galectin-3 low ) as has been reported by others 17,26,27 suggesting that Ly-6G 17 Expression of other surface markers by OMs and BM-derived macrophages is shown in supplemental Figure 3. Interestingly, the expression of CD169 did not discriminate between OMs and BM-derived macrophages because both groups of cells expressed this marker (Figure 2).…”

“…14 Furthermore, several groups have shown that macrophages are involved in HSC regulatory networks [15][16][17] and the production of reactive oxygen species. 18 Although bone marrow (BM)-derived macrophages express F4/80 (in addition to other markers, including CD45, CD68 [microsialin], CD169, and variable amounts of CD11b), it is unknown whether BM-derived macrophages and OMs (defined as bone-associated CD45…”

Hematopoietic Stem Cell Regulation by Type I and II Interferons in the Pathogenesis of Acquired Aplastic Anemia

“…(90)]. IFNγ stimulates MΦ cytokine production (Figure 1f) and antigen presentation (91), therefore, it stands to reason that MΦs may contribute to IFNγ-driven AA pathogenesis.…”

Shedding light on HSC dormancy—a role for the DARC

“…MΦs are emerging as important regulators of HSC function and location in adult bone marrow (5,(30)(31)(32)(33). To specifically test whether DARC + MΦ depletion regulates CD82 expression, the authors administered Clodronate-loaded liposomes (Clod-lip).…”

“…Hematopoietic demands that occur as a result of injury or infection must interrupt dormancy-enforcing programs. As MΦs are important immune sentinels, the study suggests MΦs may directly control HSC function in demand-adapted hematopoiesis and in conditions of acute or chronic inflammation (5). Thus, the insights provided by Hur et al have broad implications for understanding HSC function in demandadapted hematopoiesis, as well as aging and cancer.…”