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Signal Transduction and Targeted Therapy Oct 2021Varying differentiation of myeloid cells is common in tumors, inflammation, autoimmune diseases, and metabolic diseases. The release of cytokines from myeloid cells is... (Review)
Review
Varying differentiation of myeloid cells is common in tumors, inflammation, autoimmune diseases, and metabolic diseases. The release of cytokines from myeloid cells is an important driving factor that leads to severe COVID-19 cases and subsequent death. This review briefly summarizes the results of single-cell sequencing of peripheral blood, lung tissue, and cerebrospinal fluid of COVID-19 patients and describes the differentiation trajectory of myeloid cells in patients. Moreover, we describe the function and mechanism of abnormal differentiation of myeloid cells to promote disease progression. Targeting myeloid cell-derived cytokines or checkpoints is essential in developing a combined therapeutic strategy for patients with severe COVID-19.
Topics: Animals; COVID-19; Cell Differentiation; Cellular Microenvironment; Humans; Myeloid Cells; SARS-CoV-2; Single-Cell Analysis
PubMed: 34707085
DOI: 10.1038/s41392-021-00792-0 -
Journal of Leukocyte Biology Nov 2022PMN-MDSC are pathologically activated neutrophils that acquire T cell (and NK cell) suppressive activity and thus function as negative regulators of effector lymphocytes...
PMN-MDSC are pathologically activated neutrophils that acquire T cell (and NK cell) suppressive activity and thus function as negative regulators of effector lymphocytes in many disease conditions. For many years, these PMN-MDSC have mainly been seen as contributors to disease progression and severity, best exemplified in the context of cancer. However, more recently, PMN-MDSC have also been described in newborn mice and humans. This finding raised the question on the potential functional roles of these regulatory myeloid cells in neonate immunobiology. During the first days (mice) or weeks (human) of life, an initial seeding of microbiota in the gut takes place. The appearance of these microbiota triggers immune responses that could potentially lead to harmful inflammation and immunopathology. In this early phase of life, PMN-MDSC could be beneficial by limiting overshooting immune responses. Indeed, a recent paper by He et al. describes the transient presence of PMN-MDSC during the first month of life. Such PMN-MDSC have been shown to suppress T cells in a contact-depended manner, but the mechanism behind the transitory nature of this phenomenon has not yet been elucidated. In this issue of the Journal of Leukocyte Biology Perego et al. describe molecular mechanisms that regulate this transient increase and subsequent decrease of PMN-MDSC in newborn mice..
Topics: Infant, Newborn; Humans; Mice; Animals; Myeloid-Derived Suppressor Cells; Myeloid Cells; Neoplasms; T-Lymphocytes; Neutrophils
PubMed: 35946321
DOI: 10.1002/JLB.3CE0522-283R -
Biology of the Cell Apr 2020The effects of cell size, shape and deformability on cellular function have long been a topic of interest. Recently, mechanical phenotyping technologies capable of... (Review)
Review
The effects of cell size, shape and deformability on cellular function have long been a topic of interest. Recently, mechanical phenotyping technologies capable of analysing large numbers of cells in real time have become available. This has important implications for biology and medicine, especially haemato-oncology and immunology, as immune cell mechanical phenotyping, immunologic function, and malignant cell transformation are closely linked and potentially exploitable to develop new diagnostics and therapeutics. In this review, we introduce the technologies used to analyse cellular mechanical properties and review emerging findings following the advent of high throughput deformability cytometry. We largely focus on cells from the myeloid lineage, which are derived from the bone marrow and include macrophages, granulocytes and erythrocytes. We highlight advances in mechanical phenotyping of cells in suspension that are revealing novel signatures of human blood diseases and providing new insights into pathogenesis of these diseases. The contributions of mechanical phenotyping of cells in suspension to our understanding of drug mechanisms, identification of novel therapeutics and monitoring of treatment efficacy particularly in instances of haematologic diseases are reviewed, and we suggest emerging topics of study to explore as high throughput deformability cytometers become prevalent in laboratories across the globe.
Topics: Antineoplastic Agents; Biomechanical Phenomena; Elasticity; Flow Cytometry; Glucocorticoids; Humans; Microscopy, Atomic Force; Myeloid Cells; Neoplasms; Phenotype
PubMed: 31916263
DOI: 10.1111/boc.201900084 -
Annals of the New York Academy of... Sep 2021On May 2017, the World Health Organization recognized sepsis as a global health priority. Sepsis profoundly perturbs immune homeostasis by initiating a complex response... (Review)
Review
On May 2017, the World Health Organization recognized sepsis as a global health priority. Sepsis profoundly perturbs immune homeostasis by initiating a complex response that varies over time, with the concomitant occurrence of pro- and anti-inflammatory mechanisms. Sepsis deeply impacts myeloid cell response. Different mechanisms are at play, such as apoptosis, endotoxin tolerance, metabolic failure, epigenetic reprogramming, and central regulation. This induces systemic effects on circulating immune cells and impacts progenitors locally in lymphoid organs. In the bone marrow, a progressive shift toward the release of immature myeloid cells (including myeloid-derived suppressor cells), at the expense of mature neutrophils, takes place. Circulating dendritic cell number remains dramatically low and monocytes/macrophages display an anti-inflammatory phenotype and reduced antigen presentation capacity. Intensity and persistence of these alterations are associated with increased risk of deleterious outcomes in patients. Thus, myeloid cells dysfunctions play a prominent role in the occurrence of sepsis-acquired immunodeficiency. For the most immunosuppressed patients, this paves the way for clinical trials evaluating immunoadjuvant molecules (granulocyte-macrophage colony-stimulating factor and interferon gamma) aimed at restoring homeostatic myeloid cell response. Our review offers a summary of sepsis-induced myeloid cell dysfunctions and current therapeutic strategies proposed to target these defects in patients.
Topics: Animals; Biomarkers; Disease Susceptibility; Humans; Immunocompromised Host; Immunologic Deficiency Syndromes; Myeloid Cells; Myeloid-Derived Suppressor Cells; Organ Specificity; Sepsis
PubMed: 32202669
DOI: 10.1111/nyas.14333 -
Current Opinion in Hematology Jul 2022Myeloid cells - granulocytes, monocytes, macrophages and dendritic cells (DCs) - are innate immune cells that play key roles in pathogen defense and inflammation, as... (Review)
Review
PURPOSE OF REVIEW
Myeloid cells - granulocytes, monocytes, macrophages and dendritic cells (DCs) - are innate immune cells that play key roles in pathogen defense and inflammation, as well as in tissue homeostasis and repair. Over the past 5 years, in part due to more widespread use of single cell omics technologies, it has become evident that these cell types are significantly more heterogeneous than was previously appreciated. In this review, we consider recent studies that have demonstrated heterogeneity among neutrophils, monocytes, macrophages and DCs in mice and humans. We also discuss studies that have revealed the sources of their heterogeneity.
RECENT FINDINGS
Recent studies have confirmed that ontogeny is a key determinant of diversity, with specific subsets of myeloid cells arising from distinct progenitors. However, diverse microenvironmental cues also strongly influence myeloid fate and function. Accumulating evidence therefore suggests that a combination of these mechanisms underlies myeloid cell diversity.
SUMMARY
Consideration of the heterogeneity of myeloid cells is critical for understanding their diverse activities, such as the role of macrophages in tissue damage versus repair, or tumor growth versus elimination. Insights into these mechanisms are informing the design of novel therapeutic approaches.
Topics: Animals; Dendritic Cells; Granulocytes; Humans; Inflammation; Macrophages; Mice; Monocytes; Myeloid Cells
PubMed: 35285448
DOI: 10.1097/MOH.0000000000000716 -
Current Opinion in Cell Biology Feb 2024Tissue-resident myeloid cells sense and transduce mechanical signals such as stiffness, stretch and compression. In the past two years, our understanding of the... (Review)
Review
Tissue-resident myeloid cells sense and transduce mechanical signals such as stiffness, stretch and compression. In the past two years, our understanding of the mechanosensitive signalling pathways in myeloid cells has significantly expanded. Moreover, it is increasingly clear which mechanical signals induce myeloid cells towards a pro- or anti-inflammatory phenotype. This is especially relevant in the context of altered matrix mechanics in immune-related pathologies or in the response to implanted biomaterials. A detailed understanding of myeloid cell mechanosensing may eventually lead to more effective cell-based immunotherapies for cancer, the development of mechanically inspired therapies to target fibrosis, and the engineering of safer implants. This review covers these recent advances in the emerging field of mechanoimmunology of myeloid cells.
Topics: Humans; Signal Transduction; Neoplasms; Biophysics; Myeloid Cells; Mechanotransduction, Cellular
PubMed: 38176349
DOI: 10.1016/j.ceb.2023.102311 -
Cells Aug 2022The azanucleosides decitabine and azacytidine are used widely in the treatment of myeloid neoplasia and increasingly in the context of combination therapies. Although... (Review)
Review
The azanucleosides decitabine and azacytidine are used widely in the treatment of myeloid neoplasia and increasingly in the context of combination therapies. Although they were long regarded as being largely interchangeable in their function as hypomethylating agents, the azanucleosides actually have different mechanisms of action; decitabine interferes primarily with the methylation of DNA and azacytidine with that of RNA. Here, we examine the role of DNA methylation in the lineage commitment of stem cells during normal hematopoiesis and consider how mutations in epigenetic regulators such as and can lead to clonal expansion and subsequent neoplastic progression. We also consider why the efficacy of azanucleoside treatment is not limited to neoplasias carrying mutations in epigenetic regulators. Finally, we summarise recent data describing a role for azacytidine-sensitive RNA methylation in lineage commitment and in the cellular response to stress. By summarising and interpreting evidence for azanucleoside involvement in a range of cellular processes, our review is intended to illustrate the need to consider multiple modes of action in the design and stratification of future combination therapies.
Topics: Azacitidine; DNA Methylation; Decitabine; Myeloid Cells; RNA
PubMed: 36010665
DOI: 10.3390/cells11162589 -
Advances in Immunology 2020Immune responses are often accompanied by radical changes of cellular metabolism of immune cells. On the other hand, an ever increasing number of metabolic pathways and... (Review)
Review
Immune responses are often accompanied by radical changes of cellular metabolism of immune cells. On the other hand, an ever increasing number of metabolic pathways and products have been found to possess immune regulatory functions. The field of immunometabolism that investigates the interplay between metabolism and immunity has developed rapidly during the past decade. In this chapter, we attempt to summarize the recent progresses by scientists in China on metabolic regulation of innate immunity from the following three perspectives: metabolic regulation of myeloid cell functions, metabolic adaptations of tissue resident myeloid cells, and metabolism and immunity at the mucosal surfaces.
Topics: Adipose Tissue; Animals; Energy Metabolism; Fatty Liver; Humans; Immunity, Innate; Intestinal Mucosa; Kupffer Cells; Macrophages; Metabolic Networks and Pathways; Myeloid Cells; Tumor Microenvironment
PubMed: 32081196
DOI: 10.1016/bs.ai.2019.11.005 -
Frontiers in Immunology 2023Adipose tissue inflammation has been implicated in various chronic inflammatory diseases and cancer. Perivascular adipose tissue (PVAT) surrounds the aorta as an extra... (Review)
Review
Adipose tissue inflammation has been implicated in various chronic inflammatory diseases and cancer. Perivascular adipose tissue (PVAT) surrounds the aorta as an extra layer and was suggested to contribute to atherosclerosis development. PVAT regulates the function of endothelial and vascular smooth muscle cells in the aorta and represent a reservoir for various immune cells which may participate in aortic inflammation. Recent studies demonstrate that adipocytes also express various cytokine receptors and, therefore, may directly respond to inflammatory stimuli. Here we will summarize current knowledge on immune mechanisms regulating adipocyte activation and the crosstalk between myeloid cells and adipocytes in pathogenesis of atherosclerosis.
Topics: Humans; Adipose Tissue; Adipocytes; Atherosclerosis; Inflammation; Myeloid Cells
PubMed: 37781401
DOI: 10.3389/fimmu.2023.1238664 -
Clinical Journal of the American... Feb 2022Kidney homeostasis is highly dependent upon the correct functioning of myeloid cells. These cells form a distributed surveillance network throughout the kidney, where... (Review)
Review
Kidney homeostasis is highly dependent upon the correct functioning of myeloid cells. These cells form a distributed surveillance network throughout the kidney, where they play an integral role in the response to organ threat. Dysregulation of resident proinflammatory and profibrotic macrophages leads to kidney structural damage and scarring after kidney injury. Fibrosis throughout the kidney parenchyma contributes to the progressive functional decline observed in CKD, independent of the etiology. Circulating myeloid cells bearing intrinsic defects also affect the kidney substructures, such as neutrophils activated by autoantibodies that cause GN in ANCA-associated vasculitis. The kidney can also be affected by disorders of myelopoiesis, including myeloid leukemias (acute and chronic myeloid leukemias) and myelodysplastic syndromes. Clonal hematopoiesis of indeterminate potential is a common, newly recognized premalignant clinical entity characterized by clonal expansion of hyperinflammatory myeloid lineage cells that may have significant kidney sequelae. A number of existing therapies in CKD target myeloid cells and inflammation, including glucocorticoid receptor agonists and mineralocorticoid receptor antagonists. The therapeutic indications for these and other myeloid cell-targeted treatments is poised to expand as our understanding of the myeloid-kidney interface evolves.
Topics: Humans; Kidney; Kidney Diseases; Myeloid Cells
PubMed: 34507968
DOI: 10.2215/CJN.04120321