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Frontiers in Immunology 2021Cellular associations in the bone microenvironment are involved in modulating the balance between bone remodeling and resorption, which is necessary for maintaining a... (Review)
Review
Cellular associations in the bone microenvironment are involved in modulating the balance between bone remodeling and resorption, which is necessary for maintaining a normal bone morphology. Macrophages and osteoclasts are both vital components of the bone marrow. Macrophages can interact with osteoclasts and regulate bone metabolism by secreting a variety of cytokines, which make a significant contribution to the associations. Although, recent studies have fully explored either macrophages or osteoclasts, indicating the significance of these two types of cells. However, it is of high importance to report the latest discoveries on the relationships between these two myeloid-derived cells in the field of osteoimmunology. Therefore, this paper reviews this topic from three novel aspects of the origin, polarization, and subgroups based on the previous work, to provide a reference for future research and treatment of bone-related diseases.
Topics: Animals; Cell Communication; Cell Polarity; Cytokines; Humans; Macrophages; Nitric Oxide; Osteoclasts; Reactive Oxygen Species; Tumor-Associated Macrophages
PubMed: 34925351
DOI: 10.3389/fimmu.2021.778078 -
Inflammation Feb 2019Sepsis is a systemic inflammatory response syndrome caused by infection. The core mechanism underlying sepsis is immune dysfunction, with macrophages, as important cells... (Review)
Review
Sepsis is a systemic inflammatory response syndrome caused by infection. The core mechanism underlying sepsis is immune dysfunction, with macrophages, as important cells of the innate immune system, playing an essential role. Autophagy has been shown to be closely related to inflammation and immunity, and autophagy enhancement in sepsis can play a protective role by negatively regulating abnormal macrophage activation, modulating macrophage polarization phenotype, reducing activation of the inflammasome and release of inflammatory factors, and affecting macrophage apoptosis. However, excessive autophagy may also lead to autophagic death of macrophages, which further aggravates the inflammatory response. The mechanisms underlying these functions are relatively complex and remain unclear, but may be related to a variety of signaling pathways such as NF-κB, mTOR, and PI3K/AKT. The administration of drugs to assist in the regulation of macrophage autophagy has become a novel treatment for sepsis. The present review focuses on the role and the potential mechanisms of macrophage autophagy in sepsis.
Topics: Animals; Autophagy; Humans; Immunity; Inflammation; Macrophages; Sepsis; Signal Transduction
PubMed: 30194660
DOI: 10.1007/s10753-018-0890-8 -
Frontiers in Immunology 2021Osteoimmunity is involved in regulating the balance of bone remodeling and resorption, and is essential for maintaining normal bone morphology. The interaction between... (Review)
Review
Osteoimmunity is involved in regulating the balance of bone remodeling and resorption, and is essential for maintaining normal bone morphology. The interaction between immune cells and osteoclasts in the bone marrow or joint cavity is the basis of osteoimmunity, in which the macrophage-osteoclast axis plays a vital role. Monocytes or tissue-specific macrophages (macrophages resident in tissues) are an important origin of osteoclasts in inflammatory and immune environment. Although there are many reports on macrophages and osteoclasts, there is still a lack of systematic reviews on the macrophage-osteoclast axis in osteoimmunity. Elucidating the role of the macrophage-osteoclast axis in osteoimmunity is of great significance for the research or treatment of bone damage caused by inflammation and immune diseases. In this article, we introduced in detail the concept of osteoimmunity and the mechanism and regulators of the differentiation of macrophages into osteoclasts. Furthermore, we described the role of the macrophage-osteoclast axis in typical bone damage caused by inflammation and immune diseases. These provide a clear knowledge framework for studying macrophages and osteoclasts in inflammatory and immune environments. And targeting the macrophage-osteoclast axis may be an effective strategy to treat bone damage caused by inflammation and immune diseases.
Topics: Animals; Arthritis, Rheumatoid; Bone Remodeling; Bone Resorption; Bone and Bones; Cell Differentiation; Humans; Macrophages; Osteoclasts
PubMed: 33868316
DOI: 10.3389/fimmu.2021.664871 -
Laboratory Investigation; a Journal of... Feb 2020Transient receptor ion channels have emerged as immensely important channels/receptors in diverse physiological and pathological responses. Of particular interest is the... (Review)
Review
Transient receptor ion channels have emerged as immensely important channels/receptors in diverse physiological and pathological responses. Of particular interest is the transient receptor potential channel subfamily V member 4 (TRPV4), which is a polymodal, nonselective, calcium-permeant cation channel, and is activated by both endogenous and exogenous stimuli. Both neuronal and nonneuronal cells express functional TRPV4, which is responsive to a variety of biochemical and biomechanical stimuli. Emerging discoveries have advanced our understanding of the role of macrophage TRPV4 in numerous inflammatory diseases. In lung injury, TRPV4 mediates macrophage phagocytosis, secretion of pro-resolution cytokines, and generation of reactive oxygen species. TRPV4 regulates lipid-laden macrophage foam cell formation, the hallmark of atheroinflammatory conditions, in response to matrix stiffness and lipopolysaccharide stimulation. Accumulating data also point to a role of macrophage TRPV4 in the pathogenesis of the foreign body response, a chronic inflammatory condition, through the formation of foreign body giant cells. Deletion of TRPV4 in macrophages suppresses the allergic and nonallergic itch in a mouse model, suggesting a role of TRPV4 in skin disease. Here, we discuss the current understanding of the role of macrophage TRPV4 in various inflammatory conditions.
Topics: Animals; Atherosclerosis; Fibrosis; Humans; Inflammation; Lung Diseases; Macrophages; Mice; Pruritus; TRPV Cation Channels
PubMed: 31645630
DOI: 10.1038/s41374-019-0334-6 -
Blood Oct 2023In this spotlight, we review technical issues that compromise single-cell analysis of tissue macrophages, including limited and unrepresentative yields, fragmentation... (Review)
Review
In this spotlight, we review technical issues that compromise single-cell analysis of tissue macrophages, including limited and unrepresentative yields, fragmentation and generation of remnants, and activation during tissue disaggregation. These issues may lead to a misleading definition of subpopulations of macrophages and the expression of macrophage-specific transcripts by unrelated cells. Recognition of the technical limitations of single-cell approaches is required in order to map the full spectrum of tissue-resident macrophage heterogeneity and assess its biological significance.
Topics: Artifacts; Macrophages; Histiocytes
PubMed: 37595274
DOI: 10.1182/blood.2023020597 -
Frontiers in Immunology 2019Hepatic macrophages are a remarkably heterogeneous population consisting of self-renewing tissue-resident phagocytes, termed Kupffer cells (KCs), and recruited... (Review)
Review
Hepatic macrophages are a remarkably heterogeneous population consisting of self-renewing tissue-resident phagocytes, termed Kupffer cells (KCs), and recruited macrophages derived from peritoneal cavity as well as the bone marrow. KCs are located in the liver sinusoid where they scavenge the microbe from the portal vein to maintain liver homeostasis. Liver injury may trigger hepatic recruitment of peritoneal macrophages and monocyte-derived macrophages. Studies describing macrophage accumulation have shown that hepatic macrophages are involved in the initiation and progression of various liver diseases. They act as tolerogenic antigen-presenting cells to inhibit T-cell activation by producing distinct sets of cytokines, chemokines, and mediators to maintain or resolve inflammation. Furthermore, by releasing regenerative growth factors, matrix metalloproteinase arginase, they promote tissue repair. Recent experiments found that KCs and recruited macrophages may play different roles in the development of liver disease. Given that hepatic macrophages are considerably plastic populations, their phenotypes and functions are likely switching along disease progression. In this review, we summarize current knowledge about the role of tissue-resident macrophages and recruited macrophages in pathogenesis of alcoholic liver disease (ALD), non-alcoholic steatohepatitis (NASH), viral hepatitis, and hepatocellular carcinoma (HCC).
Topics: Biomarkers; Cell Communication; Cytokines; Disease Management; Disease Susceptibility; Humans; Immunophenotyping; Kupffer Cells; Liver Diseases; Macrophages; Molecular Targeted Therapy; Phenotype
PubMed: 32047496
DOI: 10.3389/fimmu.2019.03112 -
Immunobiology Mar 2019In a diabetic milieu high levels of reactive oxygen species (ROS) are induced. This contributes to the vascular complications of diabetes. Recent studies have shown that... (Review)
Review
In a diabetic milieu high levels of reactive oxygen species (ROS) are induced. This contributes to the vascular complications of diabetes. Recent studies have shown that ROS formation is exacerbated in diabetic monocytes and macrophages due to a glycolytic metabolic shift. Macrophages are important players in the progression of diabetes and promote inflammation through the release of pro-inflammatory cytokines and proteases. Because ROS is an important mediator for the activation of pro-inflammatory signaling pathways, obesity and hyperglycemia-induced ROS production may favor induction of M1-like pro-inflammatory macrophages during diabetes onset and progression. ROS induces MAPK, STAT1, STAT6 and NFκB signaling, and interferes with macrophage differentiation via epigenetic (re)programming. Therefore, a comprehensive understanding of the impact of ROS on macrophage phenotype and function is needed in order to improve treatment of diabetes and its vascular complications. In the current comprehensive review, we dissect the role of ROS in macrophage polarization, and analyze how ROS production links metabolism and inflammation in diabetes and its complications. Finally, we discuss the contribution of ROS to the crosstalk between macrophages and endothelial cells in diabetic complications.
Topics: Animals; Diabetes Mellitus; Disease Susceptibility; Energy Metabolism; Humans; Immunomodulation; Macrophage Activation; Macrophages; Oxidative Stress; Reactive Oxygen Species; Signal Transduction
PubMed: 30739804
DOI: 10.1016/j.imbio.2018.11.010 -
Seminars in Immunology Aug 2015Macrophages display a spectrum of functional activation phenotypes depending on the composition of the microenvironment they reside in, including type of tissue/organ... (Review)
Review
Macrophages display a spectrum of functional activation phenotypes depending on the composition of the microenvironment they reside in, including type of tissue/organ and character of injurious challenge they are exposed to. Our understanding of how macrophage plasticity is regulated by the local microenvironment is still limited. Here we review and discuss the recent literature regarding the contribution of cellular metabolic pathways to the ability of the macrophage to sense the microenvironment and to alter its function. We propose that distinct alterations in the microenvironment induce a spectrum of inducible and reversible metabolic programs that might form the basis of the inducible and reversible spectrum of functional macrophage activation/polarization phenotypes. We highlight that metabolic pathways in the bidirectional communication between macrophages and stromals cells are an important component of chronic inflammatory conditions. Recent work demonstrates that inflammatory macrophage activation is tightly associated with metabolic reprogramming to aerobic glycolysis, an altered TCA cycle, and reduced mitochondrial respiration. We review cytosolic and mitochondrial mechanisms that promote initiation and maintenance of macrophage activation as they relate to increased aerobic glycolysis and highlight potential pathways through which anti-inflammatory IL-10 could promote macrophage deactivation. Finally, we propose that in addition to their role in energy generation and regulation of apoptosis, mitochondria reprogram their metabolism to also participate in regulating macrophage activation and plasticity.
Topics: Citric Acid Cycle; Glycolysis; Humans; Inflammation; Macrophage Activation; Macrophages
PubMed: 26454572
DOI: 10.1016/j.smim.2015.09.001 -
Advanced Materials (Deerfield Beach,... Mar 2021Human immune system acts as a pivotal role in the tissue homeostasis and disease progression. Immunomodulatory biomaterials that can manipulate innate immunity and... (Review)
Review
Human immune system acts as a pivotal role in the tissue homeostasis and disease progression. Immunomodulatory biomaterials that can manipulate innate immunity and adaptive immunity hold great promise for a broad range of prophylactic and therapeutic purposes. This review is focused on the design strategies and principles of immunomodulatory biomaterials from the standpoint of materials science to regulate macrophage fate, such as activation, polarization, adhesion, migration, proliferation, and secretion. It offers a comprehensive survey and discussion on the tunability of material designs regarding physical, chemical, biological, and dynamic cues for modulating macrophage immune response. The range of such tailorable cues encompasses surface properties, surface topography, materials mechanics, materials composition, and materials dynamics. The representative immunoengineering applications selected herein demonstrate how macrophage-immunomodulating biomaterials are being exploited for cancer immunotherapy, infection immunotherapy, tissue regeneration, inflammation resolution, and vaccination. A perspective on the future research directions of immunoregulatory biomaterials is also provided.
Topics: Animals; Biocompatible Materials; Humans; Immunologic Factors; Macrophages
PubMed: 33565154
DOI: 10.1002/adma.202004172 -
Annual Review of Immunology Apr 2020A striking change has happened in the field of immunology whereby specific metabolic processes have been shown to be a critical determinant of immune cell activation.... (Review)
Review
A striking change has happened in the field of immunology whereby specific metabolic processes have been shown to be a critical determinant of immune cell activation. Multiple immune receptor types rewire metabolic pathways as a key part of how they promote effector functions. Perhaps surprisingly for immunologists, the Krebs cycle has emerged as the central immunometabolic hub of the macrophage. During proinflammatory macrophage activation, there is an accumulation of the Krebs cycle intermediates succinate and citrate, and the Krebs cycle-derived metabolite itaconate. These metabolites have distinct nonmetabolic signaling roles that influence inflammatory gene expression. A key bioenergetic target for the Krebs cycle, the electron transport chain, also becomes altered, generating reactive oxygen species from Complexes I and III. Similarly, alternatively activated macrophages require α-ketoglutarate-dependent epigenetic reprogramming to elicit anti-inflammatory gene expression. In this review, we discuss these advances and speculate on the possibility of targeting these events therapeutically for inflammatory diseases.
Topics: Animals; Citric Acid Cycle; Disease Susceptibility; Energy Metabolism; Humans; Immunity; Immunomodulation; Macrophage Activation; Macrophages; Signal Transduction
PubMed: 31986069
DOI: 10.1146/annurev-immunol-081619-104850