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Frontiers in Immunology 2023cDC2s occur abundantly in peripheral tissues and arise from circulating blood cDC2s. However, the factors governing cDC2 differentiation in tissues, especially under...
cDC2s occur abundantly in peripheral tissues and arise from circulating blood cDC2s. However, the factors governing cDC2 differentiation in tissues, especially under inflammatory conditions, remained poorly defined. We here found that psoriatic cDC2s express the efferocytosis receptor Axl and exhibit a bone morphogenetic protein (BMP) and p38MAPK signaling signature. BMP7, strongly expressed within the lesional psoriatic epidermis, cooperates with canonical TGF-β1 signaling for inducing AxlcDC2s from blood cDC2s . Moreover, downstream induced p38MAPK promotes AxlcDC2s at the expense of AxlCD207 Langerhans cell differentiation from blood cDC2s. BMP7 supplementation allowed to model cDC2 generation and their further differentiation into LCs from CD34 hematopoietic progenitor cells in defined serum-free medium. Additionally, p38MAPK promoted the generation of another cDC2 subset lacking Axl but expressing the non-classical NFkB transcription factor RelB . Such RelBcDC2s occurred predominantly at dermal sites in the inflamed skin. Finally, we found that cDC2s can be induced to acquire high levels of the monocyte lineage identity factor kruppel-like-factor-4 (KLF4) along with monocyte-derived DC and macrophage phenotypic characteristics In conclusion, inflammatory and psoriatic epidermal signals instruct blood cDC2s to acquire phenotypic characteristics of several tissue-resident cell subsets.
Topics: Humans; Monocytes; Dendritic Cells; Cell Differentiation; Skin; Epidermis
PubMed: 37539048
DOI: 10.3389/fimmu.2023.1216352 -
Frontiers in Immunology 2019Small non-coding microRNAs (miRNAs) have been found to play critical roles in many biological processes by controlling gene expression at the post-transcriptional level.... (Review)
Review
Small non-coding microRNAs (miRNAs) have been found to play critical roles in many biological processes by controlling gene expression at the post-transcriptional level. They appear to fine-tune the immune response by targeting key regulatory molecules, and their abnormal expression is associated with immune-mediated inflammatory disorders. Monocytes actively contribute to tissue homeostasis by triggering acute inflammatory reactions as well as the resolution of inflammation and tissue regeneration, in case of injury or pathogen invasion. Their contribution to tissue homeostasis can have many aspects because they are able to differentiate into different cell types including macrophages, dendritic cells, and osteoclasts, which fulfill functions as different as bone remodeling and immune response. Monocytes consist of different subsets with subset-specific expression of miRNAs linked to distinct biological processes dedicated to specific roles. Therefore, understanding the role of miRNAs in the context of monocyte heterogeneity may provide clues as to which subset gives rise to which cell type in tissues. In addition, because monocytes are involved in the pathogenesis of chronic inflammation, associated with loss of tissue homeostasis and function, identifying subset-specific miRNAs might help in developing therapeutic strategies that target one subset while sparing the others. Here, we give an overview of the state-of-the-art research regarding miRNAs that are differentially expressed between monocyte subsets and how they influence monocyte functional heterogeneity in health and disease, with descriptions of specific miRNAs. We also revisit the existing miRNome data to propose a canonical signature for each subset.
Topics: Animals; Humans; MicroRNAs; Monocytes
PubMed: 31608049
DOI: 10.3389/fimmu.2019.02145 -
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 -
Aging Cell Oct 2022Aging is associated with increased monocyte production and altered monocyte function. Classical monocytes are heterogenous and a shift in their subset composition may...
Aging is associated with increased monocyte production and altered monocyte function. Classical monocytes are heterogenous and a shift in their subset composition may underlie some of their apparent functional changes during aging. We have previously shown that mouse granulocyte-monocyte progenitors (GMPs) produce "neutrophil-like" monocytes (NeuMo), whereas monocyte-dendritic cell progenitors (MDPs) produce monocyte-derived dendritic cell (moDC)-producing monocytes (DCMo). Here, we demonstrate that classical monocytes from the bone marrow of old male and female mice have higher expression of DCMo signature genes (H2-Aa, H2-Ab1, H2-Eb1, Cd74), and that more classical monocytes express MHCII and CD74 protein. Moreover, we show that bone marrow MDPs and classical monocytes from old mice yield more moDC. We also demonstrate higher expression of Aw112010 in old monocytes and that Aw112010 lncRNA activity regulates MHCII induction in macrophages, which suggests that elevated Aw112010 levels may underlie increased MHCII expression during monocyte aging. Finally, we show that classical monocyte expression of MHCII is also elevated during healthy aging in humans. Thus, aging-associated changes in monocyte production may underlie altered monocyte function and have implications for aging-associated disorders.
Topics: Animals; Female; Humans; Male; Mice; Cell Differentiation; Dendritic Cells; Macrophages; Monocytes; RNA, Long Noncoding; Histocompatibility Antigens Class II
PubMed: 36040389
DOI: 10.1111/acel.13701 -
Shock (Augusta, Ga.) Feb 2021Platelets have been shown to play an important immunomodulatory role in the pathogenesis of various diseases through their interactions with other immune and nonimmune... (Review)
Review
Platelets have been shown to play an important immunomodulatory role in the pathogenesis of various diseases through their interactions with other immune and nonimmune cells. Sepsis is a major cause of death in the United States, and many of the mechanisms driving sepsis pathology are still unresolved. Monocytes have recently received increasing attention in sepsis pathogenesis, and multiple studies have associated increased levels of platelet-monocyte aggregates observed early in sepsis with clinical outcomes in sepsis patients. These findings suggest platelet-monocyte aggregates may be an important prognostic indicator. However, the mechanisms leading to platelet interaction and aggregation with monocytes, and the effects of aggregation during sepsis are still poorly defined. There are few studies that have really investigated functions of platelets and monocytes together, despite a large body of research showing separate functions of platelets and monocytes in inflammation and immune responses during sepsis. The goal of this review is to provide insights into what we do know about mechanisms and biological meanings of platelet-monocyte interactions, as well as some of the technical challenges and limitations involved in studying this important potential mechanism in sepsis pathogenesis. Improving our understanding of platelet and monocyte biology in sepsis may result in identification of novel targets that can be used to positively affect outcomes in sepsis.
Topics: Blood Platelets; Humans; Monocytes; Platelet Aggregation; Sepsis
PubMed: 32694394
DOI: 10.1097/SHK.0000000000001619 -
Frontiers in Immunology 2021Kidney macrophages are central in kidney disease pathogenesis and have therapeutic potential in preventing tissue injury and fibrosis. Recent studies highlighted that... (Review)
Review
Kidney macrophages are central in kidney disease pathogenesis and have therapeutic potential in preventing tissue injury and fibrosis. Recent studies highlighted that kidney macrophages are notably heterogeneous immune cells that fulfill opposing functions such as clearing deposited pathogens, maintaining immune tolerance, initiating and regulating inflammatory responses, promoting kidney fibrosis, and degrading the extracellular matrix. Macrophage origins can partially explain macrophage heterogeneity in the kidneys. Circulating Ly6C monocytes are recruited to inflammatory sites by chemokines, while self-renewed kidney resident macrophages contribute to kidney repair and fibrosis. The proliferation of resident macrophages or infiltrating monocytes provides an alternative explanation of macrophage accumulation after kidney injury. In addition, dynamic Ly6C expression on infiltrating monocytes accompanies functional changes in handling kidney inflammation and fibrosis. Mechanisms underlying kidney macrophage heterogeneity, either by recruiting monocyte subpopulations, regulating macrophage polarization, or impacting distinctive macrophage functions, may help develop macrophage-targeted therapies for kidney diseases.
Topics: Animals; Biomarkers; Cell Plasticity; Disease Susceptibility; Fibrosis; High-Throughput Nucleotide Sequencing; Humans; Kidney Diseases; Macrophages; Monocytes; Organ Specificity; Single-Cell Analysis
PubMed: 34093584
DOI: 10.3389/fimmu.2021.681748 -
Clinical and Experimental Hypertension... Dec 2023To investigate the level and significance of neutrophils to high-density lipoprotein cholesterol ratio (NHR) and monocytes to high-density lipoprotein cholesterol ratio...
OBJECTIVE
To investigate the level and significance of neutrophils to high-density lipoprotein cholesterol ratio (NHR) and monocytes to high-density lipoprotein cholesterol ratio (MHR) in patients with non-dipping hypertension.
METHODS
A total of 228 patients were retrospectively enrolled in the study. They were divided into the dipping hypertension group ( = 76), the non-dipping hypertension group ( = 77) and the control group ( = 75) according to 24-h ambulatory blood pressure monitoring system (ABPM) recordings. NHR and MHR were calculated and compared statistically. Receiver operating characteristic (ROC) curve analyses were performed for NHR and MHR. Binary logistic regression analyses were introduced to investigate the independent associations of NHR and MHR with non-dipping hypertension.
RESULTS
The NHR and MHR were significantly higher in the non-dipping hypertension group compared with the control group ( = .001, < .001, respectively) and the dipping hypertension group ( = .039, = .003, respectively). According to ROC curve analyses, NHR>73.35 and MHR>7.54 were regarded as high-risk groups. The area under the curve (AUC) was 0.642 ( < .001) for NHR and 0.718 ( < .001) for MHR. In multivariate analysis, compared with NHR, only MHR was still recognized as a marker for detection of non-dipping hypertension (odds ratio [OR]: 1.208, 95% confidence interval [CI]: 1.076 to 1.356, = .001).
CONCLUSIONS
Our data indicated that not NHR but MHR as new composite marker of inflammation and lipid metabolism may predict non-dipping hypertension to some extent.
Topics: Humans; Cholesterol, HDL; Monocytes; Neutrophils; Retrospective Studies; Blood Pressure Monitoring, Ambulatory; Biomarkers; Hypertension
PubMed: 37165667
DOI: 10.1080/10641963.2023.2210785 -
The American Journal of Pathology May 2020Monocyte rolling, adhesion, and transmigration across the endothelium are mediated by specific interactions between surface adhesion molecules. This process is... (Review)
Review
Monocyte rolling, adhesion, and transmigration across the endothelium are mediated by specific interactions between surface adhesion molecules. This process is fundamental to innate immunity and to inflammatory disease, including atherosclerosis, where monocyte egress into the intimal space is central to formation of fatty plaques. Monocytes are a heterogeneous population of three distinct subsets of cells, all of which play different roles in atherosclerosis progression. However, it is not well understood how interactions between different monocyte subsets and the endothelium are regulated. Furthermore, it is appreciated that endothelial adhesion molecules are heavily N-glycosylated, but beyond regulating protein trafficking to the cell surface, whether and if so how these N-glycans contribute to monocyte recruitment is not known. This review discusses how changes in endothelial N-glycosylation may impact vascular and monocytic inflammation. It will also discuss how regulating N-glycoforms on the endothelial surface may allow for the recruitment of specific monocyte subsets to sites of inflammation, and how further understanding in this area may lead to the development of glyco-specific therapeutics in the treatment of cardiovascular disease.
Topics: Animals; Cell Adhesion Molecules; Endothelial Cells; Glycosylation; Humans; Leukocyte Rolling; Monocytes; Polysaccharides
PubMed: 32084367
DOI: 10.1016/j.ajpath.2020.01.006 -
BioMed Research International 2020The brain is the most important and complex organ in most living creatures which serves as the center of the nervous system. The function of human brain includes... (Review)
Review
The brain is the most important and complex organ in most living creatures which serves as the center of the nervous system. The function of human brain includes controlling of the motion of the body and different organs and maintaining basic homeostasis. The disorders of the brain caused by a variety of reasons often severely impact the patients' normal life or lead to death in extreme cases. Monocyte is an important immune cell which is often recruited to the brain in a number of brain disorders. However, the role of monocytes may not be simply described as beneficial or detrimental. It significantly depends on the disease models and the stages of disease progression. In this review, we summarized the current knowledge about the role of monocytes and monocyte-derived macrophages during several common brain disorders. Major focuses include ischemic stroke, Alzheimer's disease, multiple sclerosis, intracerebral hemorrhage, and insomnia. The recruitment, differentiation, and function of monocyte in these diseases are reviewed.
Topics: Animals; Brain Diseases; Cell Differentiation; Humans; Inflammation; Macrophages; Mice; Monocytes
PubMed: 32596397
DOI: 10.1155/2020/9396021 -
Frontiers in Cellular and Infection... 2020Monocytes and their derivatives, including macrophages and dendritic cells, play diverse roles in the response to fungal pathogens. Sensing of fungi by monocytes... (Review)
Review
Monocytes and their derivatives, including macrophages and dendritic cells, play diverse roles in the response to fungal pathogens. Sensing of fungi by monocytes triggers signaling pathways that mediate direct effects like phagocytosis and cytokine production. Monocytes can also present fungal antigens to elicit adaptive immune responses. These monocyte-mediated pathways may be either beneficial or harmful to the host. In some instances, fungi have developed mechanisms to evade the consequences of monocyte activation and subvert these cells to promote disease. Thus, monocytes are critically involved in mediating the outcomes of these often highly fatal infections. This review will highlight the roles of monocytes in the immune response to some of the major fungi that cause invasive human disease, including , and , and discuss potential strategies to manipulate monocyte responses in order to enhance anti-fungal immunity in susceptible hosts.
Topics: Antigens, Fungal; Fungi; Humans; Macrophages; Monocytes; Phagocytosis
PubMed: 32117808
DOI: 10.3389/fcimb.2020.00034