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Frontiers in Endocrinology 2023Macrophages/microglia are immune system defense and homeostatic cells that develop from bone marrow progenitor cells. According to the different phenotypes and immune... (Review)
Review
Macrophages/microglia are immune system defense and homeostatic cells that develop from bone marrow progenitor cells. According to the different phenotypes and immune responses of macrophages (Th1 and Th2), the two primary categories of polarized macrophages/microglia are those conventionally activated (M1) and alternatively activated (M2). Macrophage/microglial polarization is a key regulating factor in the development of inflammatory disorders, cancers, metabolic disturbances, and neural degeneration. Macrophage/microglial polarization is involved in inflammation, oxidative stress, pathological angiogenesis, and tissue healing processes in ocular diseases, particularly in diabetic retinopathy (DR). The functional phenotypes of macrophages/microglia affect disease progression and prognosis, and thus regulate the polarization or functional phenotype of microglia at different DR stages, which may offer new concepts for individualized therapy of DR. This review summarizes the involvement of macrophage/microglia polarization in physiological situations and in the pathological process of DR, and discusses the promising role of polarization in personalized treatment of DR.
Topics: Humans; Microglia; Diabetic Retinopathy; Macrophages; Inflammation; Macrophage Activation; Diabetes Mellitus
PubMed: 37842315
DOI: 10.3389/fendo.2023.1276225 -
The International Journal of... Dec 2023Ageing decreases the function of the immune system and increases susceptibility to some chronic, infectious, and autoimmune diseases. Senescence cells, which produce... (Review)
Review
Ageing decreases the function of the immune system and increases susceptibility to some chronic, infectious, and autoimmune diseases. Senescence cells, which produce senescence-associated secretory phenotypes (SASPs), can activate the innate and adaptive immune responses. Macrophages are among the most abundant innate immune cell types in senescent microenvironments. Senescence-associated macrophages, recruited by SASPs, play a vital role in establishing the essential microenvironments for maintaining tissue homeostasis. However, it's important to note that these senescence-associated macrophages can also influence senescent processes, either by enhancing or impeding the functions of tissue-resident senescent cells. In this discussion, we describe the potential targets of immunosenescence and shed light on the probable mechanisms by which macrophages influence cellular senescence. Furthermore, we analyze their dual function in both clearing senescent cells and modulating age-related diseases. This multifaceted influence operates through processes including heightened inflammation, phagocytosis, efferocytosis, and autophagy. Given the potential off-target effects and immune evasion mechanisms associated with traditional anti-ageing strategies (senolytics and senomorphics), 'resetting' immune system tolerance or targeting senescence-related macrophage functions (i.e., phagocytotic capacity and immunosurveillance) will inform treatment of age-related diseases. Therefore, we review recent advances in the use of macrophage therapeutics to treat ageing and age-associated disorders, and outline the key gaps in this field.
Topics: Immunosenescence; Cellular Senescence; Macrophages
PubMed: 37866656
DOI: 10.1016/j.biocel.2023.106479 -
Frontiers in Immunology 2023Nonalcoholic fatty liver disease (NAFLD) and its inflammatory and often progressive subtype nonalcoholic steatohepatitis (NASH), have emerged as significant contributors... (Review)
Review
Nonalcoholic fatty liver disease (NAFLD) and its inflammatory and often progressive subtype nonalcoholic steatohepatitis (NASH), have emerged as significant contributors to hepatic morbidity worldwide. The pathophysiology of NAFLD/NASH is multifaceted, variable, and remains incompletely understood. The pivotal role of liver-resident and recruited macrophages in the pathogenesis of NAFLD and NASH is widely acknowledged as a crucial factor in innate immunity. The remarkable plasticity of macrophages enables them to assume diverse activation and polarization states, dictated by their immunometabolism microenvironment and functional requirements. Recent studies in the field of immunometabolism have elucidated that alterations in the metabolic profile of macrophages can profoundly influence their activation state and functionality, thereby influencing various pathological processes. This review primarily focuses on elucidating the polarization and activation states of macrophages, highlighting the correlation between their metabolic characteristics and the transition from pro-inflammatory to anti-inflammatory phenotypes. Additionally, we explore the potential of targeting macrophage metabolism as a promising therapeutic approach for the management of NAFLD/NASH.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Macrophages; Anti-Inflammatory Agents
PubMed: 37868954
DOI: 10.3389/fimmu.2023.1257596 -
Frontiers in Immunology 2023Primary Sjögren's syndrome (pSS) is a progressive inflammatory autoimmune disease. Immune cell infiltration into glandular lobules and ducts and glandular destruction...
BACKGROUND
Primary Sjögren's syndrome (pSS) is a progressive inflammatory autoimmune disease. Immune cell infiltration into glandular lobules and ducts and glandular destruction are the pathophysiological hallmarks of pSS. Macrophages are one of the most important cells involved in the induction and regulation of an inflammatory microenvironment. Although studies have reported that an abnormal tissue microenvironment alters the metabolic reprogramming and polarisation status of macrophages, the mechanisms driving macrophage infiltration and polarisation in pSS remain unclear.
METHODS
Immune cell subsets were characterised using the single-cell RNA sequencing (scRNA-seq) data of peripheral blood mononuclear cells (PBMCs) from patients with pSS (n = 5) and healthy individuals (n = 5) in a public dataset. To evaluate macrophage infiltration and polarisation in target tissues, labial salivary gland biopsy tissues were subjected to histological staining and bulk RNA-seq (pSS samples, n = 24; non-pSS samples, n = 12). RNA-seq data were analysed for the construction of macrophage co-expression modules, enrichment of biological processes and deconvolution-based screening of immune cell types.
RESULTS
Detailed mapping of PBMCs using scRNA-seq revealed five major immune cell subsets in pSS, namely, T cells, B cells, natural killer (NK) cells, dendritic cells (DCs) and monocyte-macrophages. The monocyte-macrophage subset was large and had strong inflammatory gene signatures. This subset was found to play an important role in the generation of reactive oxygen species and communicate with other innate and adaptive immune cells. Histological staining revealed that the number of tissue-resident macrophages was high in damaged glandular tissues, with the cells persistently surrounding the tissues. Analysis of RNA-seq data using multiple algorithms demonstrated that the high abundance of pro-inflammatory M1 macrophages was accompanied by the high abundance of other infiltrating immune cells, senescence-associated secretory phenotype and evident metabolic reprogramming.
CONCLUSION
Macrophages are among the most abundant innate immune cells in PBMCs and glandular tissues in patients with pSS. A bidirectional relationship exists between macrophage polarisation and the inflammatory microenvironment, which may serve as a therapeutic target for pSS.
Topics: Humans; Salivary Glands; Sjogren's Syndrome; Transcriptome; Leukocytes, Mononuclear; Macrophages
PubMed: 38022546
DOI: 10.3389/fimmu.2023.1292146 -
Journal of Translational Medicine Dec 2023AMP-activated protein kinase (AMPK) is a ubiquitous sensor of energy and nutritional status in eukaryotic cells. It plays a key role in regulating cellular energy... (Review)
Review
AMP-activated protein kinase (AMPK) is a ubiquitous sensor of energy and nutritional status in eukaryotic cells. It plays a key role in regulating cellular energy homeostasis and multiple aspects of cell metabolism. During macrophage polarisation, AMPK not only guides the metabolic programming of macrophages, but also counter-regulates the inflammatory function of macrophages and promotes their polarisation toward the anti-inflammatory phenotype. AMPK is located at the intersection of macrophage metabolism and inflammation. The metabolic characteristics of macrophages are closely related to immune-related diseases, infectious diseases, cancer progression and immunotherapy. This review discusses the structure of AMPK and its role in the metabolism, function and polarisation of macrophages. In addition, it summarises the important role of the AMPK pathway and AMPK activators in the development of macrophage-related diseases.
Topics: Humans; AMP-Activated Protein Kinases; Macrophages; Inflammation; Anti-Inflammatory Agents; Homeostasis; Energy Metabolism
PubMed: 38066566
DOI: 10.1186/s12967-023-04772-6 -
Apoptosis : An International Journal on... Dec 2023Pulmonary fibrosis (PF) is a disease in which excessive extracellular matrix (ECM) accumulation occurs in pulmonary mesenchyme, which induces the destruction of alveolar... (Review)
Review
Pulmonary fibrosis (PF) is a disease in which excessive extracellular matrix (ECM) accumulation occurs in pulmonary mesenchyme, which induces the destruction of alveolar structures and poor prognosis. Macrophage death is responsible for ECM accumulation after alveolar epithelial injury in PF. Depending on the local micro-environments, macrophages can be polarized to either classically activated (M1) or alternatively activated (M2) macrophage phenotypes. In general, M1 macrophages can promote inflammation and sterilization, stop the continuous damage process and prevent excessive repair, while M2 macrophages are anti-inflammatory and promote tissue repair, and excessive M2 macrophage activity may inhibit the absorption and degradation of ECM. Emerging evidence has revealed that death forms such as pyroptosis mediated by inflammasome affect polarization direction and ultimately lead to the development of PF. Pharmacological manipulation of macrophages death signals may serve as a logical therapeutic strategy for PF. This review will focus on the current state of knowledge regarding the regulation and underlying mechanisms of macrophages and their mediators in the influence of macrophage death on the development of PF. We expect to provide help in developing effective therapeutic strategies in clinical settings.
Topics: Humans; Macrophages, Alveolar; Pulmonary Fibrosis; Apoptosis; Macrophages; Inflammation
PubMed: 37707713
DOI: 10.1007/s10495-023-01888-4 -
Basic Research in Cardiology Feb 2024Despite the advances in treatment options, cardiovascular disease (CVDs) remains the leading cause of death over the world. Chronic inflammatory response and... (Review)
Review
Despite the advances in treatment options, cardiovascular disease (CVDs) remains the leading cause of death over the world. Chronic inflammatory response and irreversible fibrosis are the main underlying pathophysiological causes of progression of CVDs. In recent decades, cardiac macrophages have been recognized as main regulatory players in the development of these complex pathophysiological conditions. Numerous approaches aimed at macrophages have been devised, leading to novel prospects for therapeutic interventions. Our review covers the advancements in macrophage-centric treatment plans for various pathologic conditions and examines the potential consequences and obstacles of employing macrophage-targeted techniques in cardiac diseases.
Topics: Humans; Cardiovascular Diseases; Myocardial Infarction; Macrophages; Heart; Inflammation
PubMed: 38170281
DOI: 10.1007/s00395-023-01027-9 -
Immunological Reviews Aug 2023Our laboratory has a long-standing research interest in understanding how lipid-activated transcription factors, nuclear hormone receptors, contribute to dendritic cell... (Review)
Review
Our laboratory has a long-standing research interest in understanding how lipid-activated transcription factors, nuclear hormone receptors, contribute to dendritic cell and macrophage gene expression regulation, subtype specification, and responses to a changing extra and intracellular milieu. This journey in the last more than two decades took us from identifying target genes for various RXR heterodimers to systematically mapping nuclear receptor-mediated pathways in dendritic cells to identifying hierarchies of transcription factors in alternative polarization in macrophages to broaden the role of nuclear receptors beyond strictly ligand-regulated gene expression. We detail here the milestones of the road traveled and draw conclusions regarding the unexpectedly broad role of nuclear hormone receptors as epigenomic components of dendritic cell and macrophage gene regulation as we are getting ready for the next challenges.
Topics: Humans; Epigenomics; Receptors, Cytoplasmic and Nuclear; Gene Expression Regulation; Macrophages; Transcription Factors
PubMed: 37074820
DOI: 10.1111/imr.13209 -
Inflammation Research : Official... Jan 2024Emerging studies have revealed that macrophages possess different dependences on the uptake, synthesis, and metabolism of serine for their activation and... (Review)
Review
OBJECTIVE
Emerging studies have revealed that macrophages possess different dependences on the uptake, synthesis, and metabolism of serine for their activation and functionalization, necessitating our insight into how serine availability and utilization impact macrophage activation and inflammatory responses.
METHODS
This article summarizes the reports published domestically and internationally about the serine uptake, synthesis, and metabolic flux by the macrophages polarizing with distinct stimuli and under different pathologic conditions, and particularly analyzes how altered serine metabolism rewires the metabolic behaviors of polarizing macrophages and their genetic and epigenetic reprogramming.
RESULTS
Macrophages dynamically change serine metabolism to orchestrate their anabolism, redox balance, mitochondrial function, epigenetics, and post-translation modification, and thus match the distinct needs for both classical and alternative activation.
CONCLUSION
Serine metabolism coordinates multiple metabolic pathways to tailor macrophage polarization and their responses to different pathogenic attacks and thus holds the potential as therapeutic target for types of acute and chronic inflammatory diseases.
Topics: Macrophage Activation; Macrophages; Metabolic Networks and Pathways; Epigenesis, Genetic
PubMed: 38070057
DOI: 10.1007/s00011-023-01815-y -
Cell Death & Disease Aug 2023Liver regeneration is a dynamic and regulated process that involves inflammation, granulation, and tissue remodeling. Hepatic macrophages, abundantly distributed in the... (Review)
Review
Liver regeneration is a dynamic and regulated process that involves inflammation, granulation, and tissue remodeling. Hepatic macrophages, abundantly distributed in the liver, are essential components that actively participate in each step to orchestrate liver regeneration. In the homeostatic liver, resident macrophages (Kupffer cells) acquire a tolerogenic phenotype and contribute to immunological tolerance. Following toxicity-induced damage or physical resection, Kupffer cells as well as monocyte-derived macrophages can be activated and promote an inflammatory process that supports the survival and activation of hepatic myofibroblasts and thus promotes scar tissue formation. Subsequently, these macrophages, in turn, exhibit the anti-inflammatory effects critical to extracellular matrix remodeling during the resolution stage. However, continuous damage-induced chronic inflammation generally leads to hepatic macrophage dysfunction, which exacerbates hepatocellular injury and triggers further liver fibrosis and even cirrhosis. Emerging macrophage-targeting strategies have shown efficacy in both preclinical and clinical studies. Increasing evidence indicates that metabolic rewiring provides substrates for epigenetic modification, which endows monocytes/macrophages with prolonged "innate immune memory". Therefore, it is reasonable to conceive novel therapeutic strategies for metabolically reprogramming macrophages and thus mediate a homeostatic or reparative process for hepatic inflammation management and liver regeneration.
Topics: Humans; Kupffer Cells; Liver Regeneration; Macrophages; Homeostasis; Liver Cirrhosis; Inflammation
PubMed: 37644019
DOI: 10.1038/s41419-023-06066-7