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Cell Reports Oct 2021In emergency myelopoiesis (EM), expansion of the myeloid progenitor compartment and increased myeloid cell production are observed and often mediated by the...
In emergency myelopoiesis (EM), expansion of the myeloid progenitor compartment and increased myeloid cell production are observed and often mediated by the pro-inflammatory cytokine interferon gamma (IFN-γ). Interleukin-10 (IL-10) inhibits IFN-γ secretion, but paradoxically, its therapeutic administration to humans causes hematologic changes similar to those observed in EM. In this work, we use different in vivo systems, including a humanized immune system mouse model, to show that IL-10 triggers EM, with a significant expansion of the myeloid progenitor compartment and production of myeloid cells. Hematopoietic progenitors display a prominent IFN-γ transcriptional signature, and we show that IFN-γ mediates IL-10-driven EM. We also find that IL-10, unexpectedly, reprograms CD4 and CD8 T cells toward an activation state that includes IFN-γ production by these T cell subsets in vivo. Therefore, in addition to its established anti-inflammatory properties, IL-10 can induce IFN-γ production and EM, opening additional perspectives for the design of IL-10-based immunotherapies.
Topics: Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Interferon-gamma; Interleukin-10; Mice; Mice, Knockout; Myeloid Progenitor Cells; Myelopoiesis
PubMed: 34706233
DOI: 10.1016/j.celrep.2021.109887 -
Current Opinion in Hematology Jan 2018The purpose of this review is to describe recent findings in the context of previous work regarding dysregulated myelopoiesis and hematopoietic function following an... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to describe recent findings in the context of previous work regarding dysregulated myelopoiesis and hematopoietic function following an acute physiologic insult, focusing on the expansion and persistence of myeloid-deriver suppressor cells, the deterioration of lymphocyte number and function, and the inadequacy of stress erythropoiesis.
RECENT FINDINGS
Persistent myeloid-derived suppressor cell (MDSC) expansion among critically ill septic patients is associated with T-cell suppression, vulnerability to nosocomial infection, chronic critical illness, and poor long-term functional status. Multiple approaches targeting MDSC expansion and suppressor cell activity may serve as a primary or adjunctive therapeutic intervention. Traumatic injury and the neuroendocrine stress response suppress bone marrow erythropoietin receptor expression in a process that may be reversed by nonselective beta-adrenergic receptor blockade. Hepcidin-mediated iron-restricted anemia of critical illness requires further investigation of novel approaches involving erythropoiesis-stimulating agents, iron administration, and hepcidin modulation.
SUMMARY
Emergency myelopoiesis is a dynamic process with unique phenotypes for different physiologic insults and host factors. Following an acute physiologic insult, critically ill patients are subject to persistent MDSC expansion, deterioration of lymphocyte number and function, and inadequate stress erythropoiesis. Better strategies are required to identify patients who are most likely to benefit from targeted therapies.
Topics: Animals; Hematopoiesis; Humans; Lymphocytes; Myelopoiesis
PubMed: 29035909
DOI: 10.1097/MOH.0000000000000395 -
Journal of Innate Immunity 2018An intact and fully functional innate immune system is critical in the defense against pathogens. Indeed, during systemic infection, the ability of the organism to cope... (Review)
Review
An intact and fully functional innate immune system is critical in the defense against pathogens. Indeed, during systemic infection, the ability of the organism to cope with the increased demand for phagocytes depends heavily on sufficient replenishment of mature myeloid cells. This process, designated emergency or demand-adapted myelopoiesis, requires the activation of hematopoietic progenitors in the bone marrow (BM), resulting in their proliferation and differentiation toward the myeloid lineage. Failure of BM progenitors to adapt to the enhanced need for mature cells in the periphery can be life-threatening, as indicated by the detrimental effect of chemotherapy-induced myelosuppression on the outcome of systemic infection. Recent advances demonstrate an important role of not only committed myeloid progenitors but also of hematopoietic stem cells (HSCs) in emergency myelopoiesis. In this regard, pathogen-derived products (e.g., Toll-like receptor ligands) activate HSC differentiation towards the myeloid lineage, either directly or indirectly, by inducing the production of inflammatory mediators (e.g., cytokines and growth factors) by hematopoietic and nonhematopoietic cell populations. The inflammatory mediators driving demand-adapted myelopoiesis target not only HSCs but also HSC-supportive cell populations, collectively known as the HSC niche, the microenvironment where HSCs reside. In this review, we discuss recent findings that have further elucidated the mechanisms that drive emergency myelopoiesis, focusing on the interactions of HSCs with their BM microenvironment.
Topics: Animals; Bone Marrow Cells; Cell Differentiation; Hematopoietic Stem Cells; Humans; Immunity, Innate; Myelopoiesis; Stem Cell Niche
PubMed: 29874678
DOI: 10.1159/000489406 -
Cell Metabolism May 2014Ongoing monocyte infiltration and subsequent macrophage seeding of adipose tissue is thought to be a key feature of obesity pathophysiology. Nagareddy et al. (2014)...
Ongoing monocyte infiltration and subsequent macrophage seeding of adipose tissue is thought to be a key feature of obesity pathophysiology. Nagareddy et al. (2014) show that adipose cells locally activate IL-1β in macrophages in part through the alarmin S100A8/A9, which stimulates bone marrow myelopoiesis to perpetuate nonresolving inflammation.
Topics: Adipose Tissue; Animals; Humans; Macrophages; Male; Monocytes; Myelopoiesis; Obesity
PubMed: 24807218
DOI: 10.1016/j.cmet.2014.04.010 -
International Immunology May 2023The microbiota engages in the development and maintenance of the host immune system. The microbiota affects not only mucosal tissues where it localizes but also the... (Review)
Review
The microbiota engages in the development and maintenance of the host immune system. The microbiota affects not only mucosal tissues where it localizes but also the distal organs. Myeloid cells are essential for host defense as first responders of the host immune system. Their generation, called myelopoiesis, is regulated by environmental signals, including commensal microbiota. Hematopoietic stem and progenitor cells in bone marrow can directly or indirectly sense microbiota-derived signals, thereby giving rise to myeloid cell lineages at steady-state and during inflammation. In this review, we discuss the role of commensal microorganisms in the homeostatic regulation of myelopoiesis in the bone marrow. We also outline the effects of microbial signals on myelopoiesis during inflammation and infection, with a particular focus on the development of innate immune memory. Studying the relationship between the microbiota and myelopoiesis will help us understand how the microbiota regulates immune responses at a systemic level beyond the local mucosa.
Topics: Humans; Myelopoiesis; Inflammation; Bone Marrow; Microbiota; Homeostasis
PubMed: 36694400
DOI: 10.1093/intimm/dxad002 -
Frontiers in Immunology 2019Monocytes are a subset of cells that are categorized together with dendritic cells (DCs) and macrophages in the mononuclear phagocyte system (MPS). Despite sharing... (Review)
Review
Monocytes are a subset of cells that are categorized together with dendritic cells (DCs) and macrophages in the mononuclear phagocyte system (MPS). Despite sharing several phenotypic and functional characteristics with MPS cells, monocytes are unique cells with the ability to function as both precursor and effector cells in their own right. Before the development of hematopoietic stem cells (HSCs) , monocytes are derived from erythro-myeloid precursors (EMPs) in the fetal liver that are important for populating the majority of tissue resident macrophages. After birth, monocytes arise from bone marrow (BM)-derived HSCs and are released into the circulation upon their maturation, where they survey peripheral tissues and maintain endothelial integrity. Upon sensing of microbial breaches or inflammatory stimuli, monocytes migrate into tissues where their plasticity allows them to differentiate into cells that resemble macrophages or DCs according to the environmental niche. Alternatively, they may also migrate into tissues in the absence of inflammation and remain in an undifferentiated state where they perform homeostatic roles. As monocytes are typically on the move, the availability of intravital imaging approaches has provided further insights into their trafficking patterns in distinct tissue compartments. In this review, we outline the importance of understanding their functional behavior in the context of tissue compartments, and how these studies may contribute towards improved vaccine and future therapeutic strategies.
Topics: Animals; Cardiovascular System; Cell Movement; Fetus; Humans; Leukopoiesis; Monocytes; Spatio-Temporal Analysis
PubMed: 31040854
DOI: 10.3389/fimmu.2019.00834 -
Frontiers in Immunology 2019Blood monocytes develop in the bone marrow before being released into the peripheral circulation. The circulating monocyte pool is composed of multiple subsets, each... (Review)
Review
Blood monocytes develop in the bone marrow before being released into the peripheral circulation. The circulating monocyte pool is composed of multiple subsets, each with specialized functions. These cells are recruited to repopulate resident monocyte-derived cells in the periphery and also to sites of injury. Several extrinsic factors influence the function and quantity of monocytes in the blood. Here, we outline the impact of sex, ethnicity, age, sleep, diet, and exercise on monocyte subsets and their function, highlighting that steady state is not a single physiological condition. A clearer understanding of the relationship between these factors and the immune system may allow for improved therapeutic strategies.
Topics: Aging; Animals; Environment; Ethnicity; Exercise; Homeostasis; Humans; Inheritance Patterns; Leukopoiesis; Life Style; Monocytes; Sex Characteristics; Sleep
PubMed: 31787976
DOI: 10.3389/fimmu.2019.02581 -
Innate Immunity Apr 2014Proper development and activation of cells of the myeloid lineage are critical for supporting innate immunity. This myelopoiesis is orchestrated by interdependent... (Review)
Review
Proper development and activation of cells of the myeloid lineage are critical for supporting innate immunity. This myelopoiesis is orchestrated by interdependent interactions between cytokine receptors, transcription factors and, as recently described, microRNAs (miRNAs). miRNAs contribute to normal and dysregulated myelopoiesis. Alterations in myelopoiesis underlie myeloid-derived suppressor cell (MDSC) expansion, a poorly understood heterogeneous population of immature and suppressive myeloid cells that expand in nearly all diseases where inflammation exists. MDSCs associated with inflammation often have immunosuppressive properties, but molecular mechanisms responsible for MDSC expansion are unclear. Emerging data implicate miRNAs in MDSC expansion. This review focuses on miRNAs that contribute to myeloid lineage differentiation and maturation under physiological conditions, and introduces the concept that altered miRNA expression my underlie expansion and accumulation of MDSCs. We divide our miRNAs into those with potential to promote MDSC expansion and two with known direct links to MDSC expansion, miR-223 and miR-494.
Topics: Animals; Cell Proliferation; Humans; Immunity, Innate; MicroRNAs; Myeloid Cells; Myelopoiesis
PubMed: 23757323
DOI: 10.1177/1753425913489850 -
Frontiers in Immunology 2020Myeloid cells are key components of the tumor microenvironment and critical regulators of disease progression. These innate immune cells are usually short-lived and... (Review)
Review
Myeloid cells are key components of the tumor microenvironment and critical regulators of disease progression. These innate immune cells are usually short-lived and require constant replenishment. Emerging evidence indicates that tumors alter the host hematopoietic system and induce the biased differentiation of myeloid cells to tip the balance of the systemic immune activities toward tumor-promoting functions. Altered myelopoiesis is not restricted to the bone marrow and also occurs in extramedullary organs. In this review, we outline the recent advances in the field of cancer-associated myelopoiesis, with a focus on the spleen, the major site of extramedullary hematopoiesis in the cancer setting. We discuss the functional specialization, distinct mechanisms, and clinical relevance of cancer-associated myeloid cell generation from early progenitors in the spleen and its potential as a novel therapeutic target.
Topics: Animals; Humans; Myeloid Cells; Myeloid Progenitor Cells; Myelopoiesis; Neoplasms; Spleen
PubMed: 32582203
DOI: 10.3389/fimmu.2020.01126 -
Advances in Wound Care Nov 2022Emerging evidence has shown a link between the status of hematopoietic stem cells (HSCs) and wound healing responses. Thus, better understanding HSCs will contribute to...
Emerging evidence has shown a link between the status of hematopoietic stem cells (HSCs) and wound healing responses. Thus, better understanding HSCs will contribute to further advances in wound healing research. Myeloid cells such as neutrophils and monocyte-derived macrophages are critical players in the process of wound healing. HSCs actively respond to wound injury and other tissue insults, including infection and produce the effector myeloid cells, and a failing of the HSC response can result in impaired wound healing. Technological advances such as transcriptome at single-cell resolution, epigenetics, three-dimensional imaging, transgenic animals, and animal models, have provided novel concepts of myeloid generation (myelopoiesis) from HSCs, and have revealed cell-intrinsic and -extrinsic mechanisms that can impact HSC functions in the context of health conditions. The newer concepts include-the programmed cellular fate at a differentiation stage that is used to be considered as the multilineage, the signaling pathways that can activate HSCs directly and indirectly, the mechanisms that can deteriorate HSCs, the roles and remodeling of the surrounding environment for HSCs and their progenitors (the niche). The researches on HSCs, which produce blood cells, should contribute to the development of blood biomarkers predicting a risk of chronic wounds, which may transform clinical practice of wound care with precision medicine for patients at high risk of poor healing.
Topics: Animals; Cell Differentiation; Hematopoietic Stem Cells; Myeloid Cells; Myelopoiesis; Wound Healing
PubMed: 34353116
DOI: 10.1089/wound.2021.0065