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Proceedings of the National Academy of... Apr 2023Multiple sclerosis (MS) is an incurable autoimmune disease and is currently treated by systemic immunosuppressants with off-target side effects. Although aberrant...
Multiple sclerosis (MS) is an incurable autoimmune disease and is currently treated by systemic immunosuppressants with off-target side effects. Although aberrant myeloid function is often observed in MS plaques in the central nervous system (CNS), the role of myeloid cells in therapeutic intervention is currently overlooked. Here, we developed a myeloid cell-based strategy to reduce the disease burden in experimental autoimmune encephalomyelitis (EAE), a mouse model of progressive MS. We developed monocyte-adhered microparticles ("backpacks") for activating myeloid cell phenotype to an anti-inflammatory state through localized interleukin-4 and dexamethasone signals. We demonstrate that backpack-laden monocytes infiltrated into the inflamed CNS and modulated both the local and systemic immune responses. Within the CNS, backpack-carrying monocytes regulated both the infiltrating and tissue-resident myeloid cell compartments in the spinal cord for functions related to antigen presentation and reactive species production. Treatment with backpack-monocytes also decreased the level of systemic pro-inflammatory cytokines. Additionally, backpack-laden monocytes induced modulatory effects on T1 and T17 populations in the spinal cord and blood, demonstrating cross talk between the myeloid and lymphoid arms of disease. Backpack-carrying monocytes conferred therapeutic benefit in EAE mice, as quantified by improved motor function. The use of backpack-laden monocytes offers an antigen-free, biomaterial-based approach to precisely tune cell phenotype in vivo, demonstrating the utility of myeloid cells as a therapeutic modality and target.
Topics: Mice; Animals; Multiple Sclerosis; Myeloid Cells; Encephalomyelitis, Autoimmune, Experimental; Central Nervous System; Monocytes; Mice, Inbred C57BL
PubMed: 37075071
DOI: 10.1073/pnas.2221535120 -
Histology and Histopathology Apr 2016Multiple sclerosis (MS) is a demyelinating disease in which an exacerbated immune response provokes oligodendrocyte loss and demyelination, the hallmarks of this... (Review)
Review
Multiple sclerosis (MS) is a demyelinating disease in which an exacerbated immune response provokes oligodendrocyte loss and demyelination, the hallmarks of this neurological disease. The destruction of myelin due to the uncontrolled activity of the invading immune cells leads to the formation of MS plaques. Among the different leukocytes that participate in the immune response associated with MS, the role of myeloid cells has been analyzed extensively (i.e. macrophages, dendritic cells -DCs- and neutrophils). Hence, in this review we will summarize what is known about the distribution, expression and markers available to study myeloid cells, and their histopathology, not only in a standard animal model of MS (autoimmune experimental encephalomyelitis -EAE) but also in MS tissue. In this review, we will not only refer to mature myeloid cells but also to the undifferentiated and almost unexplored myeloid-derived suppressor cells (MDSCs). The active role of MDSCs in the prompt resolution of an immune episode is gaining importance, yet is still the subject of some debate. Finally, the similarities and differences between MS and EAE are discussed, particularly in terms of myeloid cell phenotype, activity and the markers used.
Topics: Animals; Encephalomyelitis, Autoimmune, Experimental; Humans; Multiple Sclerosis; Myeloid Cells
PubMed: 26592711
DOI: 10.14670/HH-11-699 -
Expert Review of Anticancer Therapy 2023Studies have shown that myeloma cell leukemia-1 (MCL-1) is associated with the prognosis of patients with cancer. To further validate the prognostic value of MCL-1 in... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Studies have shown that myeloma cell leukemia-1 (MCL-1) is associated with the prognosis of patients with cancer. To further validate the prognostic value of MCL-1 in cancer, a meta-analysis was conducted.
METHODS
Six databases were searched using Boolean logic search formulas. Data were extracted from the included literature, and pooled odds ratio, hazard ratio, and 95% confidence interval were calculated to determine the relationship between MCL-1 levels and clinicopathological characteristics and prognosis of patients with cancer. When heterogeneity was found to be significant, a random effects model was used, otherwise, a fixed effects model was used.
RESULTS
Twelve articles were included in this meta-analysis, totaling 2208 patients with cancer across 14 studies. A high MCL-1 expression level was associated with patients with high T stage, M stage, and TNM stage in some cancers. Additionally, high MCL-1 expression was likely to be observed in patients with poorly differentiated digestive system tumors and patients with lung adenocarcinoma. Notably, a higher expression of MCL-1 was found to be associated with shorter overall survival in patients with hematological tumors, digestive system tumors, and lung cancer.
CONCLUSION
MCL-1 may be a prognostic biomarker in patients with some types of cancer.
Topics: Humans; Biomarkers, Tumor; Digestive System Neoplasms; Leukemia; Myeloid Cell Leukemia Sequence 1 Protein; Myeloid Cells; Prognosis
PubMed: 37467344
DOI: 10.1080/14737140.2023.2238900 -
Nature Neuroscience Sep 2018Innate immune cells recruited to inflammatory sites have short life spans and originate from the marrow, which is distributed throughout the long and flat bones. While...
Innate immune cells recruited to inflammatory sites have short life spans and originate from the marrow, which is distributed throughout the long and flat bones. While bone marrow production and release of leukocyte increases after stroke, it is currently unknown whether its activity rises homogeneously throughout the entire hematopoietic system. To address this question, we employed spectrally resolved in vivo cell labeling in the murine skull and tibia. We show that in murine models of stroke and aseptic meningitis, skull bone marrow-derived neutrophils are more likely to migrate to the adjacent brain tissue than cells that reside in the tibia. Confocal microscopy of the skull-dura interface revealed myeloid cell migration through microscopic vascular channels crossing the inner skull cortex. These observations point to a direct local interaction between the brain and the skull bone marrow through the meninges.
Topics: Adult; Animals; Bone Marrow; Cell Movement; Female; Humans; Inflammation; Male; Meningitis, Aseptic; Mice; Mice, Inbred C57BL; Middle Aged; Myeloid Cells; Neutrophils; Skull; Stroke; Tibia; Tomography, X-Ray Computed
PubMed: 30150661
DOI: 10.1038/s41593-018-0213-2 -
Frontiers in Immunology 2019The myeloid cell system shows very high plasticity, which is crucial to quickly adapt to changes during an immune response. From the beginning, this high plasticity has... (Review)
Review
The myeloid cell system shows very high plasticity, which is crucial to quickly adapt to changes during an immune response. From the beginning, this high plasticity has made cell type classification within the myeloid cell system difficult. Not surprising, naming schemes have been frequently changed. Recent advancements in multidimensional technologies, including mass cytometry and single-cell RNA sequencing, are challenging our current understanding of cell types, cell subsets, and functional states of cells. Despite the power of these technologies to create new reference maps for the myeloid cell system, it is essential to put these new results into context with previous knowledge that was established over decades. Here we report on earlier attempts of cell type classification in the myeloid cell system, discuss current approaches and their pros and cons, and propose future strategies for cell type classification within the myeloid cell system that can be easily extended to other cell types.
Topics: Animals; Cell Plasticity; Cell Shape; Flow Cytometry; Humans; Myeloid Cells; Sequence Analysis, RNA
PubMed: 31636632
DOI: 10.3389/fimmu.2019.02287 -
Cytokine & Growth Factor Reviews Oct 2020Interferon regulatory factors (IRFs) are a family of central transcriptional regulators that produce type I interferon and regulate innate and adaptive immune responses.... (Review)
Review
Interferon regulatory factors (IRFs) are a family of central transcriptional regulators that produce type I interferon and regulate innate and adaptive immune responses. Interferon regulatory factor 8 (IRF8) exists mainly in hematopoietic cells and is essential for the development of several myeloid lineages, including monocytes/macrophages and dendritic cells. In recent years, an increasing number of studies have focused on the roles of IRF8 in the differentiation of myeloid pedigree and MDSC aggregation in diseases such as tumors. In this review, we provide a comprehensive overview of the roles of IRF8 in the regulation of myeloid cell development, with particular reference to multiple disease conditions. Clarifying the various functions of IRF8 may suggest targets for therapeutic interventions.
Topics: Cell Differentiation; Hematopoiesis; Interferon Regulatory Factors; Myeloid Cells
PubMed: 32327344
DOI: 10.1016/j.cytogfr.2020.03.003 -
European Journal of Immunology Aug 2015Tuberculosis (TB), a chronic bacterial infectious disease caused by Mycobacterium tuberculosis (Mtb), typically affects the lung and causes profound morbidity and... (Review)
Review
Tuberculosis (TB), a chronic bacterial infectious disease caused by Mycobacterium tuberculosis (Mtb), typically affects the lung and causes profound morbidity and mortality rates worldwide. Recent advances in cellular immunology emphasize the complexity of myeloid cell subsets controlling TB inflammation. The specialization of myeloid cell subsets for particular immune processes has tailored their roles in protection and pathology. Among myeloid cells, dendritic cells (DCs) are essential for the induction of adaptive immunity, macrophages predominantly harbor Mtb within TB granulomas and polymorphonuclear neutrophils (PMNs) orchestrate lung damage. However, within each myeloid cell population, diverse phenotypes with unique functions are currently recognized, differentially influencing TB pneumonia and granuloma functionality. More recently, myeloid-derived suppressor cells (MDSCs) have been identified at the site of Mtb infection. Along with PMNs, MDSCs accumulate within the inflamed lung, interact with granuloma-residing cells and contribute to exuberant inflammation. In this review, we discuss the contribution of different myeloid cell subsets to inflammation in TB by highlighting their interactions with Mtb and their role in lung pathology. Uncovering the manifold nature of myeloid cells in TB pathogenesis will inform the development of future immune therapies aimed at tipping the inflammation balance to the benefit of the host.
Topics: Animals; Dendritic Cells; Granuloma, Respiratory Tract; Humans; Mycobacterium tuberculosis; Myeloid Cells; Tuberculosis, Pulmonary
PubMed: 26140356
DOI: 10.1002/eji.201545493 -
Frontiers in Immunology 2024
Topics: Humans; Cellular Reprogramming; Myeloid Cells; Animals; Signal Transduction
PubMed: 38745655
DOI: 10.3389/fimmu.2024.1414482 -
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 -
Breast Cancer Research : BCR Jun 2023Breast cancer presents as one of the top health threats to women around the world. Myeloid cells are the most abundant cells and the major immune coordinator in breast...
BACKGROUND
Breast cancer presents as one of the top health threats to women around the world. Myeloid cells are the most abundant cells and the major immune coordinator in breast cancer tumor microenvironment (TME), target therapies that harness the anti-tumor potential of myeloid cells are currently being evaluated in clinical trials. However, the landscape and dynamic transition of myeloid cells in breast cancer TME are still largely unknown.
METHODS
Myeloid cells were characterized in the single-cell data and extracted with a deconvolution algorithm to be assessed in bulk-sequencing data. We used the Shannon index to describe the diversity of infiltrating myeloid cells. A 5-gene surrogate scoring system was then constructed and evaluated to infer the myeloid cell diversity in a clinically feasible manner.
RESULTS
We dissected the breast cancer infiltrating myeloid cells into 15 subgroups including macrophages, dendritic cells (DCs), and monocytes. Mac_CCL4 had the highest angiogenic activity, Mac_APOE and Mac_CXCL10 were highly active in cytokine secretion, and the DCs had upregulated antigen presentation pathways. The infiltrating myeloid diversity was calculated in the deconvoluted bulk-sequencing data, and we found that higher myeloid diversity was robustly associated with more favorable clinical outcomes, higher neoadjuvant therapy responses, and a higher rate of somatic mutations. We then used machine learning methods to perform feature selection and reduction, which generated a clinical-friendly scoring system consisting of 5 genes (C3, CD27, GFPT2, GMFG, and HLA-DPB1) that could be used to predict clinical outcomes in breast cancer patients.
CONCLUSIONS
Our study explored the heterogeneity and plasticity of breast cancer infiltrating myeloid cells. By using a novel combination of bioinformatic approaches, we proposed the myeloid diversity index as a new prognostic metric and constructed a clinically practical scoring system to guide future patient evaluation and risk stratification.
Topics: Humans; Female; Breast Neoplasms; Myeloid Cells; Macrophages; Monocytes; Prognosis; Tumor Microenvironment
PubMed: 37287069
DOI: 10.1186/s13058-023-01669-6