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Frontiers in Immunology 2024
Topics: Humans; Cellular Reprogramming; Myeloid Cells; Animals; Signal Transduction
PubMed: 38745655
DOI: 10.3389/fimmu.2024.1414482 -
European Journal of Immunology Oct 2023Experimental autoimmune encephalomyelitis (EAE) is an animal model of central nervous system (CNS) autoimmunity. It is most commonly used to mimic aspects of multiple... (Review)
Review
Experimental autoimmune encephalomyelitis (EAE) is an animal model of central nervous system (CNS) autoimmunity. It is most commonly used to mimic aspects of multiple sclerosis (MS), a demyelinating disorder of the human brain and spinal cord. The innate immune response displays one of the core pathophysiological features linked to both the acute and chronic stages of MS. Hence, understanding and targeting the innate immune response is essential. Microglia and other CNS resident MUs, as well as infiltrating myeloid cells, diverge substantially in terms of both their biology and their roles in EAE. Recent advances in the field show that antigen presentation, as well as disease-propagating and regulatory interactions with lymphocytes, can be attributed to specific myeloid cell types and cell states in EAE lesions, following a distinct temporal pattern during disease initiation, propagation and recovery. Furthermore, single-cell techniques enable the assessment of characteristic proinflammatory as well as beneficial cell states, and identification of potential treatment targets. Here, we discuss the principles of EAE induction and protocols for varying experimental paradigms, the composition of the myeloid compartment of the CNS during health and disease, and systematically review effects on myeloid cells for therapeutic approaches in EAE.
Topics: Animals; Humans; Mice; Encephalomyelitis, Autoimmune, Experimental; Central Nervous System; Multiple Sclerosis; Spinal Cord; Myeloid Cells; Mice, Inbred C57BL
PubMed: 37505465
DOI: 10.1002/eji.202250234 -
Advances in Immunology 2023Myeloid cells, particularly macrophages, act as the frontline responders to infectious agents and initiate inflammation. While the molecular mechanisms driving... (Review)
Review
Myeloid cells, particularly macrophages, act as the frontline responders to infectious agents and initiate inflammation. While the molecular mechanisms driving inflammatory responses have primarily focused on pattern recognition by myeloid cells and subsequent transcriptional events, it is crucial to note that post-transcriptional regulation plays a pivotal role in this process. In addition to the transcriptional regulation of innate immune responses, additional layers of intricate network of post-transcriptional mechanisms critically determine the quantity and duration of key inflammatory products and thus the outcome of immune responses. A multitude of mechanisms governing post-transcriptional regulation in innate immunity have been uncovered, encompassing RNA alternative splicing, mRNA stability, and translational regulation. This review encapsulates the current insights into the post-transcriptional regulation of inflammatory genes within myeloid cells, with particular emphasis on translational regulation during inflammation. While acknowledging the advancements, we also shed light on the existing gaps in immunological research pertaining to post-transcriptional levels and propose perspectives that controlling post-transcriptional process may serve as potential targets for therapeutic interventions in inflammatory diseases.
Topics: Humans; Immunity, Innate; Inflammation; Myeloid Cells; Macrophages; Alternative Splicing
PubMed: 38042586
DOI: 10.1016/bs.ai.2023.09.001 -
International Journal of Hematology Apr 2015
Topics: Gene Expression Regulation, Developmental; Hematopoiesis; Humans; Myeloid Cells; Transcriptional Activation
PubMed: 25753224
DOI: 10.1007/s12185-015-1770-8 -
Frontiers in Immunology 2020Amino acid metabolism is a critical regulator of the immune response, and its modulating becomes a promising approach in various forms of immunotherapy. Insufficient... (Review)
Review
Amino acid metabolism is a critical regulator of the immune response, and its modulating becomes a promising approach in various forms of immunotherapy. Insufficient concentrations of essential amino acids restrict T-cells activation and proliferation. However, only arginases, that degrade L-arginine, as well as enzymes that hydrolyze L-tryptophan are substantially increased in cancer. Two arginase isoforms, ARG1 and ARG2, have been found to be present in tumors and their increased activity usually correlates with more advanced disease and worse clinical prognosis. Nearly all types of myeloid cells were reported to produce arginases and the increased numbers of various populations of myeloid-derived suppressor cells and macrophages correlate with inferior clinical outcomes of cancer patients. Here, we describe the role of arginases produced by myeloid cells in regulating various populations of immune cells, discuss molecular mechanisms of immunoregulatory processes involving L-arginine metabolism and outline therapeutic approaches to mitigate the negative effects of arginases on antitumor immune response. Development of potent arginase inhibitors, with improved pharmacokinetic properties, may lead to the elaboration of novel therapeutic strategies based on targeting immunoregulatory pathways controlled by L-arginine degradation.
Topics: Animals; Antineoplastic Agents; Arginase; Arginine; Clinical Trials as Topic; Humans; Macrophages; Mice; Myeloid Cells; Myeloid Progenitor Cells; Neoplasms
PubMed: 32499785
DOI: 10.3389/fimmu.2020.00938 -
Nature Communications Nov 2023Disease-modifying therapies (DMTs) are widely used in neuroimmunological diseases such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD)....
Disease-modifying therapies (DMTs) are widely used in neuroimmunological diseases such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Although these treatments are known to predispose patients to infections and affect their responses to vaccination, little is known about the impact of DMTs on the myeloid cell compartment. In this study, we use mass cytometry to examine DMT-associated changes in the innate immune system in untreated and treated patients with MS (n = 39) or NMOSD (n = 23). We also investigated the association between changes in myeloid cell phenotypes and longitudinal responsiveness to homologous primary, secondary, and tertiary SARS-CoV-2 mRNA vaccinations. Multiple DMT-associated myeloid cell clusters, in particular CD64HLADR granulocytes, showed significant correlations with B and T cell responses induced by vaccination. Our findings suggest the potential role of myeloid cells in cellular and humoral responses following vaccination in DMT-treated patients with neuroimmunological diseases.
Topics: Humans; Myeloid Cells; Granulocytes; Myeloid Progenitor Cells; Vaccination; Multiple Sclerosis; Neuromyelitis Optica; Antibodies, Viral
PubMed: 38007484
DOI: 10.1038/s41467-023-43553-z -
Cellular Immunology Aug 2018Tumors of various histological origins show abundant infiltration of myeloid cells from early stages of disease progression. These cells have a profound impact on... (Review)
Review
Tumors of various histological origins show abundant infiltration of myeloid cells from early stages of disease progression. These cells have a profound impact on antitumor immunity and influence fundamental processes that underlie malignancy, including neoangiogenesis, sustained cancer cell proliferation, metastasis and therapy resistance. For these reasons, development of therapeutic approaches to deplete or reprogram myeloid cells in cancer is an emerging field of interest. However, knowledge about the heterogeneity of myeloid cells in tumors and their variability between patients and disease stages is still limited. In this review, we summarize the most recent advances in our understanding about how the phenotype of tumor-associated macrophages, monocytes, neutrophils, myeloid-derived suppressor cells and dendritic cells is dictated by their ontogeny, activation status and localization. We also outline major open questions that will only be resolved by applying high-dimensional single-cell technologies and systems biology approaches in the analysis of the tumor microenvironment.
Topics: Animals; Cell Proliferation; Dendritic Cells; Humans; Macrophages; Monocytes; Myeloid Cells; Neoplasms; Neutrophils; Tumor Microenvironment
PubMed: 29482836
DOI: 10.1016/j.cellimm.2018.02.008 -
Microbiology Spectrum Jan 2017The inflammasome is a large multimeric protein complex comprising an effector protein that demonstrates specificity for a variety of activators or ligands; an adaptor... (Review)
Review
The inflammasome is a large multimeric protein complex comprising an effector protein that demonstrates specificity for a variety of activators or ligands; an adaptor molecule; and procaspase-1, which is converted to caspase-1 upon inflammasome activation. Inflammasomes are expressed primarily by myeloid cells and are located within the cell. The macromolecular inflammasome structure can be visualized by cryo-electron microscopy. This complex has been found to play a role in a variety of disease models in mice, and several have been genetically linked to human diseases. In most cases, the effector protein is a member of the NLR (nucleotide-binding domain leucine-rich repeat-containing) or NOD (nucleotide oligomerization domain)-like receptor protein family. However, other effectors have also been described, with the most notable being AIM-2 (absent in melanoma 2), which recognizes DNA to elicit inflammasome function. This review will focus on the role of the inflammasome in myeloid cells and its role in health and disease.
Topics: Animals; Humans; Inflammasomes; Myeloid Cells
PubMed: 28102121
DOI: 10.1128/microbiolspec.MCHD-0049-2016 -
Energy metabolism drives myeloid-derived suppressor cell differentiation and functions in pathology.Journal of Leukocyte Biology Aug 2017Over the last decade, a heterogeneous population of immature myeloid cells with major regulatory functions has been described in cancer and other pathologic conditions... (Review)
Review
Over the last decade, a heterogeneous population of immature myeloid cells with major regulatory functions has been described in cancer and other pathologic conditions and ultimately defined as MDSCs. Most of the early work on the origins and functions of MDSCs has been in murine and human tumor bearers in which MDSCs are known to be immunosuppressive and to result in both reduced immune surveillance and antitumor cytotoxicity. More recent studies, however, suggest that expansion of these immature myeloid cells may be linked to most, if not all, chronic and acute inflammatory processes. The universal expansion to inflammatory stimuli of MDSCs suggests that these cells may be more of a normal component of the inflammatory response (emergency myelopoiesis) than simply a pathologic response to a growing tumor. Instead of an adverse immunosuppressive response, expansion of these immature myeloid cell populations may result from a complex balance between increased immune surveillance and dampened adaptive immune responses that are common to many inflammatory responses. Within this scenario, new pathways of metabolic reprogramming are emerging as drivers of MDSC differentiation and functions in cancer and inflammatory disorders, crucially linking metabolic syndrome to inflammatory processes.
Topics: Animals; Cell Differentiation; Energy Metabolism; Humans; Myeloid-Derived Suppressor Cells
PubMed: 28223316
DOI: 10.1189/jlb.4MR1116-476R -
Nature Reviews. Rheumatology May 2019Systemic sclerosis (SSc) is an autoimmune fibrotic disease of unknown aetiology that is characterized by vascular changes in the skin and visceral organs. Autologous... (Review)
Review
Systemic sclerosis (SSc) is an autoimmune fibrotic disease of unknown aetiology that is characterized by vascular changes in the skin and visceral organs. Autologous haematopoietic stem cell transplantation can improve skin and organ fibrosis in patients with progressive disease and a high risk of organ failure, indicating that cells originating in the bone marrow are important contributors to the pathogenesis of SSc. Animal studies also indicate a pivotal function of myeloid cells in the development of fibrosis leading to changes in the tissue architecture and dysfunction in multiple organs such as the heart, lungs, liver and kidney. In this Review, we summarize current knowledge about the function of myeloid cells in fibrogenesis that occurs in patients with SSc. Targeted therapies currently in clinical studies for SSc might affect myeloid cell-related pathways. Therefore, myeloid cells might be used as cellular biomarkers of disease through the application of high-dimensional techniques such as mass cytometry and single-cell RNA sequencing.
Topics: Animals; Fibrosis; Humans; Myeloid Cells; Scleroderma, Systemic
PubMed: 30953037
DOI: 10.1038/s41584-019-0212-z