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Immunity Feb 2019Myelopoiesis ensures the steady state of the myeloid cell compartment. Technological advances in fate mapping and genetic engineering, as well as the advent of single... (Review)
Review
Myelopoiesis ensures the steady state of the myeloid cell compartment. Technological advances in fate mapping and genetic engineering, as well as the advent of single cell RNA-sequencing, have highlighted the heterogeneity of the hematopoietic system and revealed new concepts in myeloid cell ontogeny. These technologies are also shedding light on mechanisms of myelopoiesis at homeostasis and at different phases of infection and inflammation, illustrating important feedback loops between affected tissues and the bone marrow. We review these findings here and revisit principles in myelopoiesis in light of the evolving understanding of myeloid cell ontogeny and heterogeneity. We argue for the importance of system-wide evaluation of changes in myelopoiesis and discuss how even after the resolution of inflammation, long-lasting alterations in myelopoiesis may play a role in innate immune memory or trained immunity.
Topics: Animals; Bone Marrow; Homeostasis; Humans; Immunity, Innate; Infections; Inflammation; Models, Immunological; Myeloid Cells; Myeloid Progenitor Cells; Myelopoiesis
PubMed: 30784577
DOI: 10.1016/j.immuni.2019.01.019 -
Cell Regeneration (London, England) Jan 2023Myelopoiesis is the process in which the mature myeloid cells, including monocytes/macrophages and granulocytes, are developed. Irregular myelopoiesis may cause and... (Review)
Review
Myelopoiesis is the process in which the mature myeloid cells, including monocytes/macrophages and granulocytes, are developed. Irregular myelopoiesis may cause and deteriorate a variety of hematopoietic malignancies such as leukemia. Myeloid cells and their precursors are difficult to capture in circulation, let alone observe them in real time. For decades, researchers had to face these difficulties, particularly in in-vivo studies. As a unique animal model, zebrafish possesses numerous advantages like body transparency and convenient genetic manipulation, which is very suitable in myelopoiesis research. Here we review current knowledge on the origin and regulation of myeloid development and how zebrafish models were applied in these studies.
PubMed: 36595106
DOI: 10.1186/s13619-022-00139-2 -
Nature Immunology Jan 2022Anemia is a major comorbidity in aging, chronic kidney and inflammatory diseases, and hematologic malignancies. However, the transcriptomic networks governing...
Anemia is a major comorbidity in aging, chronic kidney and inflammatory diseases, and hematologic malignancies. However, the transcriptomic networks governing hematopoietic differentiation in blood cell development remain incompletely defined. Here we report that the atypical kinase RIOK2 (right open reading frame kinase 2) is a master transcription factor (TF) that not only drives erythroid differentiation, but also simultaneously suppresses megakaryopoiesis and myelopoiesis in primary human stem and progenitor cells. Our study reveals the previously uncharacterized winged helix-turn-helix DNA-binding domain and two transactivation domains of RIOK2 that are critical to regulate key hematopoietic TFs GATA1, GATA2, SPI1, RUNX3 and KLF1. This establishes RIOK2 as an integral component of the transcriptional regulatory network governing human hematopoietic differentiation. Importantly, RIOK2 mRNA expression significantly correlates with these TFs and other hematopoietic genes in myelodysplastic syndromes, acute myeloid leukemia and chronic kidney disease. Further investigation of RIOK2-mediated transcriptional pathways should yield therapeutic approaches to correct defective hematopoiesis in hematologic disorders.
Topics: Amino Acid Sequence; Blood Cells; Cell Differentiation; Cell Line, Tumor; Cells, Cultured; Erythropoiesis; Gene Expression Regulation; HEK293 Cells; Hematopoietic Stem Cells; Humans; K562 Cells; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Myelopoiesis; Protein Serine-Threonine Kinases; Transcription Factors; Transcription, Genetic
PubMed: 34937919
DOI: 10.1038/s41590-021-01079-w -
Current Osteoporosis Reports Feb 2020We reviewed recent progress on the role of sclerostin (SOST) and its effects on the immune system in order to summarize the current state of knowledge in... (Review)
Review
PURPOSE OF REVIEW
We reviewed recent progress on the role of sclerostin (SOST) and its effects on the immune system in order to summarize the current state of knowledge in osteoimmunology, in regard to hematopoiesis, lymphopoiesis, and inflammation.
RECENT FINDINGS
Changes in sclerostin levels affect distinct niches within the bone marrow that support hematopoietic stem cells and B cell development. Sclerostin's regulation of adipogenesis could also be important for immune cell maintenance with age. Surprisingly, B cell development in the bone marrow is influenced by Sost produced by mesenchymal stem cells and osteoblasts, but not by osteocytes. Additionally, extramedullary hematopoiesis in the spleen and increased pro-inflammatory cytokine levels in the bone marrow are observed in global Sost mice. In addition to changes in bone marrow density, sclerostin depletion affects B lymphopoiesis and myelopoiesis, as well as other changes within the bone marrow cavity that could affect hematopoiesis. It is therefore important to monitor for hematopoietic changes in patients receiving sclerostin-depleting therapies.
Topics: Adaptor Proteins, Signal Transducing; Adipogenesis; Animals; B-Lymphocytes; Bone Marrow; Cytokines; Hematopoiesis; Hematopoiesis, Extramedullary; Hematopoietic Stem Cells; Humans; Lymphopoiesis; Mesenchymal Stem Cells; Mice; Mice, Knockout; Myelopoiesis; Osteoblasts; Osteocytes
PubMed: 31970653
DOI: 10.1007/s11914-020-00563-w -
Trends in Molecular Medicine May 2019In contrast to traditional immune cell-centered viewpoints, recent studies suggest that tissues are not passive recipients of immunity but have a 'regulatory say' over... (Review)
Review
In contrast to traditional immune cell-centered viewpoints, recent studies suggest that tissues are not passive recipients of immunity but have a 'regulatory say' over the host inflammatory response. Identification of tissue-derived homeostatic molecules regulating immune plasticity is seminal for understanding the inherent regulatory potential of different organs in the immune response. DEL-1 (developmental endothelial locus-1) is a secreted multidomain protein interacting with integrins and phospholipids and regulates, depending on its expression location, distinct stages of the host inflammatory response (from myelopoiesis over leukocyte recruitment to efferocytosis and resolution of inflammation). Here we synthesize recent evidence of DEL-1 as an exemplar local regulatory factor in the context of tissue immune plasticity and inflammatory disorders (such as periodontitis, multiple sclerosis, and pulmonary disorders), and discuss its potential as a therapeutic agent.
Topics: Animals; Calcium-Binding Proteins; Cell Adhesion Molecules; Cell Plasticity; Chemotaxis, Leukocyte; Disease Susceptibility; Homeostasis; Humans; Immunomodulation; Inflammation; Myelopoiesis; Neutrophils; Organ Specificity; Phagocytosis; Protein Binding; Signal Transduction; Structure-Activity Relationship
PubMed: 30885428
DOI: 10.1016/j.molmed.2019.02.010 -
Journal of Leukocyte Biology Nov 2016The gut microbiota is a complex and dynamic microbial ecosystem that plays a fundamental role in host physiology. Locally, the gut commensal microbes/host symbiotic... (Review)
Review
The gut microbiota is a complex and dynamic microbial ecosystem that plays a fundamental role in host physiology. Locally, the gut commensal microbes/host symbiotic relationship is vital for barrier fortification, nutrient absorption, resistance against intestinal pathogens, and the development and maintenance of the mucosal immune system. It is now clear that the effects of the indigenous intestinal flora extend beyond the gut, ranging from shaping systemic immune responses to metabolic and behavioral functions. However, the underlying mechanisms of the gut microbiota/systemic immune system interactions remain largely unknown. Myeloid cells respond to microbial signals, including those derived from commensals, and initiate innate and adaptive immune responses. In this review, we focus on the impact of the gut microbiota on myeloid cells at extraintestinal sites. In particular, we discuss how commensal-derived signals affect steady-state myelopoiesis and cellular function and how that influences the response to infection and cancer therapy.
Topics: Adaptive Immunity; Animals; Cytokines; Dysbiosis; Gastrointestinal Microbiome; Homeostasis; Humans; Immunity, Innate; Infections; Inflammation; Models, Immunological; Myeloid Cells; Myelopoiesis; Neoplasms; Neutrophils; Symbiosis; Vaccine Potency
PubMed: 27605211
DOI: 10.1189/jlb.3RI0516-222R -
Antioxidants & Redox Signaling Jul 2021Neutrophils are potent effector cells of innate immunity requiring precise regulation of their numbers and functions in blood and tissues. Macrophages have emerged as... (Review)
Review
Neutrophils are potent effector cells of innate immunity requiring precise regulation of their numbers and functions in blood and tissues. Macrophages have emerged as modulators of neutrophil properties. In inflammatory conditions, tissue macrophages modulate neutrophil trafficking and activation. Further, macrophages govern granulopoiesis in the bone marrow hematopoietic niche. Interactions of macrophages and neutrophils can be induced by cytokines and damage-associated molecular patterns, and they are also regulated by oxidative signaling. We review the impact of macrophages on neutrophil development and function, and its consequences in health and disease. Targeting the liaison between macrophages and neutrophils might provide an interesting therapeutic strategy to reduce tissue inflammation and promote immune tolerance. . 35, 182-191.
Topics: Animals; Bone Marrow; Cell Communication; Cell Differentiation; Cytokines; Hematopoietic Stem Cells; Homeostasis; Humans; Immunity, Innate; Inflammation Mediators; Macrophages; Myelopoiesis; Neutrophils; Oxidation-Reduction; Phagocytosis; Signal Transduction; Stem Cell Niche
PubMed: 33107319
DOI: 10.1089/ars.2020.8203 -
Journal of Leukocyte Biology Dec 2015Myeloid-derived suppressor cells are a heterogeneous group of pathologically activated immature cells that play a major role in the negative regulation of the immune... (Review)
Review
Myeloid-derived suppressor cells are a heterogeneous group of pathologically activated immature cells that play a major role in the negative regulation of the immune response in cancer, autoimmunity, many chronic infections, and inflammatory conditions, as well as in the regulation of tumor angiogenesis, tumor cell invasion, and metastases. Accumulation of myeloid-derived suppressor cells is governed by a network of transcriptional regulators that could be combined into 2 partially overlapping groups: factors promoting myelopoiesis and preventing differentiation of mature myeloid cells and factors promoting pathologic activation of myeloid-derived suppressor cells. In this review, we discuss the specific nature of these factors and their impact on myeloid-derived suppressor cell development.
Topics: Animals; Humans; Myeloid Cells; Myelopoiesis; Neoplasm Invasiveness; Neoplasms; Neovascularization, Pathologic; Transcription Factors; Transcription, Genetic
PubMed: 26337512
DOI: 10.1189/jlb.4RI0515-204R -
Current Opinion in Hematology Jul 2015Hematopoietic stem cells can self-renew and also give rise to the entire repertoire of hematopoietic cells. During acute infectious and inflammatory stresses, the... (Review)
Review
PURPOSE OF REVIEW
Hematopoietic stem cells can self-renew and also give rise to the entire repertoire of hematopoietic cells. During acute infectious and inflammatory stresses, the hematopoietic system can quickly adapt to demand by increasing output of innate immune cells many-fold, often at the expense of lymphopoiesis and erythropoiesis. We review recent advances in understanding the regulation of stress-induced hematopoiesis with a specific focus on the direct effects of inflammatory signaling on hematopoietic stem and progenitor cells (HSPCs).
RECENT FINDINGS
Recent studies have highlighted several areas of exciting new developments in the field, including the complex interaction and crosstalk within HSPCs and between bone marrow mesenchymal stem cells and endothelial cells needed to achieve regulated myelopoiesis, identification of increased number of inflammatory and infectious molecules with direct effects on HSPCs, the critical role of inflammatory signaling on embryonic specification of hematopoietic stem cells, and the ability of cytokines to instruct lineage choice at the HSPC level.
SUMMARY
These exciting new findings will shape our fundamental understanding of how inflammatory signaling regulates hematopoiesis in health and disease, and facilitate the development of potential interventions to treat hematologic diseases associated with altered inflammatory signaling.
Topics: Adaptation, Physiological; Cell Communication; Cell Differentiation; Cell Lineage; Cytokines; Erythropoiesis; Gene Expression Regulation; Hematologic Diseases; Hematopoietic Stem Cells; Humans; Lymphopoiesis; Myelopoiesis; Signal Transduction; Stress, Physiological; Toll-Like Receptors
PubMed: 26049748
DOI: 10.1097/MOH.0000000000000149 -
Journal of Molecular and Cellular... Feb 2024Of all the different risk factors known to cause cardiovascular disease (CVD), age and sex are considered to play a crucial role. Aging follows a continuum from birth to... (Review)
Review
Of all the different risk factors known to cause cardiovascular disease (CVD), age and sex are considered to play a crucial role. Aging follows a continuum from birth to death, and therefore it inevitably acts as a risk for CVD. Along with age, sex differences have also been shown to demonstrate variations in immune system responses to pathological insults. It has been widely perceived that females are protected against myocardial infarction (MI) and the protection is quite apparent in young vs. old women. Acute MI leads to changes in the population of myeloid and lymphoid cells at the injury site with myeloid bias being observed in the initial inflammation and the lymphoid in the late-resolution phases of the pathology. Multiple evidence demonstrates that aging enhances damage to various cellular processes through inflamm-aging, an inflammatory process identified to increase pro-inflammatory markers in circulation and tissues. Following MI, marked changes were observed in different sub-sets of major myeloid cell types viz., neutrophils, monocytes, and macrophages. There is a paucity of information regarding the tissue and site-specific functions of these sub-sets. In this review, we highlight the importance of age and sex as crucial risk factors by discussing their role during MI-induced myelopoiesis while emphasizing the current status of myeloid cell sub-sets. We further put forth the need for designing and executing age and sex interaction studies aimed to determine the appropriate age and sex to develop personalized therapeutic strategies post-MI.
Topics: Female; Humans; Male; Myelopoiesis; Myocardial Infarction; Monocytes; Macrophages; Inflammation
PubMed: 38163742
DOI: 10.1016/j.yjmcc.2023.11.011