Macrophages in immunoregulation and therapeutics

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 22, 2023

Abstract Macrophages exist in various tissues, several body cavities, and around mucosal surfaces are a vital part of the innate immune system for host defense against many pathogens cancers. possess binary M1/M2 macrophage polarization settings, which perform central role an array tasks via intrinsic signal cascades and, therefore, must be precisely regulated. Many crucial questions about signaling modulation yet to uncovered. In addition, clinical importance tumor-associated macrophages is becoming more widely recognized as significant progress has been made understanding their biology. Moreover, they integral tumor microenvironment, playing regulation wide variety processes including angiogenesis, extracellular matrix transformation, cancer cell proliferation, metastasis, immunosuppression, resistance chemotherapeutic checkpoint blockade immunotherapies. Herein, we discuss signaling, mechanical stresses modulation, metabolic pathways, mitochondrial transcriptional, epigenetic regulation. Furthermore, have broadly extended traps essential roles autophagy aging regulating functions. discussed recent advances macrophages-mediated autoimmune diseases tumorigenesis. Lastly, targeted therapy portray prospective targets therapeutic strategies health diseases.

Язык: Английский

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Metabolism of tissue macrophages in homeostasis and pathology

Cellular and Molecular Immunology, Год журнала: 2021, Номер 19(3), С. 384 - 408

Опубликована: Дек. 7, 2021

Abstract Cellular metabolism orchestrates the intricate use of tissue fuels for catabolism and anabolism to generate cellular energy structural components. The emerging field immunometabolism highlights importance maintenance activities immune cells. Macrophages are embryo- or adult bone marrow-derived leukocytes that key healthy homeostasis but can also contribute pathologies such as metabolic syndrome, atherosclerosis, fibrosis cancer. Macrophage has largely been studied in vitro. However, different organs contain diverse macrophage populations specialize distinct often tissue-specific functions. This context specificity creates diverging challenges fulfill their homeostatic roles particular microenvironment conditions response pathological conditions. Here, we outline current knowledge on requirements adaptations macrophages located tissues during selected diseases.

Язык: Английский

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Obesity I: Overview and molecular and biochemical mechanisms

Biochemical Pharmacology, Год журнала: 2022, Номер 199, С. 115012 - 115012

Опубликована: Апрель 5, 2022

Язык: Английский

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Metabolic Regulation of Macrophage Activation

Journal of Innate Immunity, Год журнала: 2021, Номер 14(1), С. 51 - 68

Опубликована: Июль 9, 2021

Macrophages, the central mediators of innate immune responses, being in first-line defense, they have to readily respond pathogenic or tissue damage signals initiate inflammatory cascade. Such rapid responses require energy support orchestrated production pro-inflammatory and activation phagocytosis. Being a cell type that is present diverse environments conditions, macrophages adapt different nutritional resources. Thus, developed plasticity are capable utilizing at both normoxic hypoxic conditions presence varying concentrations glucose other nutrients. adaptation reflected on changes signaling pathways modulate accounting for phenotypes observed. Macrophage metabolism has been tightly associated with distinct within range M1-like M2-like types. In context diseases, systemic also affect macrophage metabolism, as diabetes insulin resistance, which results altered adipose periphery. solid tumors, tumor-associated environment, metabolic an phenotype supports tumor growth. Coordination environmental determines turn shapes magnitude response. Therefore, modulating provides potential therapeutic approach diseases cancer.

Язык: Английский

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Single-cell dissection of the obesity-exercise axis in adipose-muscle tissues implies a critical role for mesenchymal stem cells

Cell Metabolism, Год журнала: 2022, Номер 34(10), С. 1578 - 1593.e6

Опубликована: Окт. 1, 2022

Exercise training is critical for the prevention and treatment of obesity, but its underlying mechanisms remain incompletely understood given challenge profiling heterogeneous effects across multiple tissues cell types. Here, we address this opposing exercise high-fat diet (HFD)-induced obesity at single-cell resolution in subcutaneous visceral white adipose tissue skeletal muscle mice with interventions. We identify a prominent role mesenchymal stem cells (MSCs) exercise-induced adaptation. Among pathways regulated by HFD MSCs three tissues, extracellular matrix remodeling circadian rhythm are most prominent. Inferred cell-cell interactions implicate within- multi-tissue crosstalk centered around MSCs. Overall, our work reveals intricacies diversity molecular responses to uncovers previously underappreciated tissue-specific beneficial exercise.

Язык: Английский

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Roles of Macrophages in Atherogenesis

Frontiers in Pharmacology, Год журнала: 2021, Номер 12

Опубликована: Ноя. 26, 2021

Atherosclerosis is a chronic inflammatory disease that may ultimately lead to local proteolysis, plaque rupture, and thrombotic vascular disease, resulting in myocardial infarction, stroke, sudden cardiac death. Circulating monocytes are recruited the arterial wall response insults differentiate into macrophages which make critical contribution tissue damage, wound healing, also regression of atherosclerotic lesions. Within plaques, take up aggregated lipoproteins have entered vessel give rise cholesterol-engorged foam cells. Also, macrophage phenotype influenced by various stimuli affect their polarization, efferocytosis, proliferation, apoptosis. The heterogeneity lesions has recently been addressed single-cell sequencing techniques. This article reviews recent advances regarding roles different stages pathogenesis from initiation advanced atherosclerosis. Macrophage-based therapies for atherosclerosis management described.

Язык: Английский

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The Obese Brain: Mechanisms of Systemic and Local Inflammation, and Interventions to Reverse the Cognitive Deficit

Frontiers in Integrative Neuroscience, Год журнала: 2022, Номер 16

Опубликована: Март 29, 2022

Overweight and obesity are now considered a worldwide pandemic growing public health problem with severe economic social consequences. Adipose tissue is an organ neuroimmune-endocrine functions, which participates in homeostasis. So, adipocyte hypertrophy hyperplasia induce state of chronic inflammation that causes changes the brain neuroinflammation. Studies obese animal models patients have shown relationship between diet cognitive decline, especially working memory learning deficiencies. Here we analyze how obesity-related peripheral can affect central nervous system physiology, generating Given blood-brain barrier interface periphery system, its altered physiology may mediate consequences on various processes. Finally, several interventions, use natural compounds exercise to prevent adverse effects also discussed.

Язык: Английский

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Regulatory T cells in skin regeneration and wound healing

Military Medical Research, Год журнала: 2023, Номер 10(1)

Опубликована: Окт. 23, 2023

Abstract As the body’s integumentary system, skin is vulnerable to injuries. The subsequent wound healing processes aim restore dermal and epidermal integrity functionality. To this end, multiple tissue-resident cells recruited immune cooperate efficiently repair injured tissue. Such temporally- spatially-coordinated interplay necessitates tight regulation prevent collateral damage such as overshooting responses excessive inflammation. In context, regulatory T (Tregs) hold a key role in balancing homeostasis mediating cutaneous healing. A comprehensive understanding of Tregs’ multifaceted field activity may help decipher pathologies and, ultimately, establish new treatment modalities. Herein, we review Tregs orchestrating regeneration adnexa catalyzing healthy repair. Further, discuss how operate during fibrosis, keloidosis, scarring.

Язык: Английский

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Adipose tissue aging is regulated by an altered immune system

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Фев. 17, 2023

Adipose tissue is a widely distributed organ that plays critical role in age-related physiological dysfunctions as an important source of chronic sterile low-grade inflammation. undergoes diverse changes during aging, including fat depot redistribution, brown and beige decrease, functional decline adipose progenitor stem cells, senescent cell accumulation, immune dysregulation. Specifically, inflammaging common aged tissue. reduces plasticity pathologically contributes to adipocyte hypertrophy, fibrosis, ultimately, dysfunction. also diseases, such diabetes, cardiovascular disease cancer. There increased infiltration cells into tissue, these infiltrating secrete proinflammatory cytokines chemokines. Several molecular signaling pathways mediate the process, JAK/STAT, NFκB JNK, etc. The roles aging are complex, underlying mechanisms remain largely unclear. In this review, we summarize consequences causes We further outline cellular/molecular propose potential therapeutic targets alleviate problems.

Язык: Английский

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Adipose tissue macrophages and their role in obesity-associated insulin resistance: an overview of the complex dynamics at play

Bioscience Reports, Год журнала: 2023, Номер 43(3)

Опубликована: Янв. 31, 2023

Obesity, a major global health concern, is characterized by serious imbalance between energy intake and expenditure leading to excess accumulation of fat in adipose tissue (AT). A state chronic low-grade AT inflammation prevalent during obesity. The macrophages (ATM) with astounding heterogeneity complex regulation play decisive role mediating obesity-induced insulin resistance. Adipose-derived were broadly classified as proinflammatory M1 anti-inflammatory M2 subtypes but recent reports have proclaimed several novel intermediate profiles, which are crucial understanding the dynamics macrophage phenotypes development Lipid-laden hypertrophic adipocytes release various chemotactic signals that aggravate infiltration into skewing toward mostly status. ratio M1-like M2-like increased substantially resulting copious secretion mediators such TNFα, IL-6, IL-1β, MCP-1, fetuin-A (FetA), etc. further worsening Several AT-derived factors could influence ATM content activation. Apart from being detrimental, exerts beneficial effects Recent studies highlighted prime AT-resident subpopulations not only effective clearance dying also controlling vascular integrity, adipocyte secretions, fibrosis within obese AT. friend or foe determined an intricate interplay arising hyperlipidemic microenvironment present review article highlights some key research advances function regulation, appreciates pathophysiologic scenario obesity-associated

Язык: Английский

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