The role of macrophages in the resolution of inflammation

Journal of Clinical Investigation, Journal Year: 2019, Volume and Issue: 129(7), P. 2619 - 2628

Published: May 19, 2019

Macrophages are tissue-resident or infiltrated immune cells critical for innate immunity, normal tissue development, homeostasis, and repair of damaged tissue. Macrophage function is a sum their ontogeny, the local environment in which they reside, type injuries pathogen to exposed. In this Review, we discuss role macrophages restoration after injury, highlighting important questions about how respond modify microenvironment restore homeostasis.

Language: Английский

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Reappraising the role of inflammation in heart failure

Nature Reviews Cardiology, Journal Year: 2020, Volume and Issue: 17(5), P. 269 - 285

Published: Jan. 22, 2020

Language: Английский

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More Than Just Attractive: How CCL2 Influences Myeloid Cell Behavior Beyond Chemotaxis

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: Dec. 13, 2019

Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) is renowned for its ability to drive the chemotaxis of myeloid and lymphoid cells. It orchestrates migration these cell types both during physiological immune defense in pathologic circumstances, such as autoimmune diseases including rheumatoid arthritis multiple sclerosis, inflammatory atherosclerosis, well infectious diseases, obesity, diabetes various cancer. However, scope CCL2’s functions extends beyond original characterization a chemoattractant. Emerging evidence shows that it impacts leukocyte behavior, influencing adhesion, polarization, effector molecule secretion, autophagy, killing survival. The direction CCL2-induced responses context dependent some cases synergistic with other stimuli. involvement CCL2 signaling renders an interesting therapeutic target, although current targeting strategies have not met early expectations clinic. A better understanding how affects cells will be pivotal improvement existing approaches, development new drugs. Here, we provide overview pleiotropic effects on lineage, chemotaxis, highlight actions help shape behavior tumor immunity.

Language: Английский

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An acute immune response underlies the benefit of cardiac stem cell therapy

Nature, Journal Year: 2019, Volume and Issue: 577(7790), P. 405 - 409

Published: Nov. 27, 2019

Language: Английский

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Obesity, Hypertension, and Cardiac Dysfunction

Circulation Research, Journal Year: 2020, Volume and Issue: 126(6), P. 789 - 806

Published: March 12, 2020

Obesity and hypertension, which often coexist, are major risk factors for heart failure characterized by chronic, low-grade inflammation, promotes adverse cardiac remodeling. While macrophages play a key role in remodeling, dysregulation of macrophage polarization between the proinflammatory M1 anti-inflammatory M2 phenotypes excessive inflammation injury. Metabolic shifting glycolysis mitochondrial oxidative phosphorylation has been implicated polarization. primarily rely on glycolysis, whereas tricarboxylic acid cycle phosphorylation; thus, that affect metabolism may disrupt M1/M2 homeostasis exacerbate inflammation. The mechanisms obesity hypertension synergistically induce metabolic dysfunction, particularly during not fully understood. We propose via directly target metabolism, including changes circulating glucose fatty substrates, lipotoxicity, tissue hypoxia. discuss canonical novel roles obesity-hypertension-induced injury, diastolic dysfunction impaired calcium handling. Finally, we current status potential therapies to failure, antidiabetic therapies, immunometabolic agents.

Language: Английский

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Cardiac monocytes and macrophages after myocardial infarction

Cardiovascular Research, Journal Year: 2019, Volume and Issue: 116(6), P. 1101 - 1112

Published: Dec. 12, 2019

Abstract Improvements in early interventions after acute myocardial infarction (AMI), notably, the increased use of timely reperfusion therapy, have survival dramatically recent decades. Despite this, maladaptive ventricular remodelling and subsequent heart failure (HF) following AMI remain a significant clinical challenge, particularly because several pre-clinical strategies to attenuate failed translate into practice. Monocytes macrophages, pleiotropic cells innate immune system, are integral both initial inflammatory response injury wound healing many tissues, including heart. However, cell behaviour contributes mouse models, prompting experimental efforts modulate prevent development HF. Seminal work macrophage biology defined macrophages as monocyte-derived that comprised two populations, pro-inflammatory M1 reparative M2 investigations cardiac populations suggested they aligned well this model. more data, other demonstrate remarkable heterogeneity plasticity development, phenotype, function. These insights may explain non-specific immunosuppressive offer novel opportunities for therapeutic targeting HF AMI. Here, we summarize traditional monocyte-macrophage paradigm, evidence significance these AMI, potential relevance emerging refutes canonical models monocyte biology.

Language: Английский

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Three tissue resident macrophage subsets coexist across organs with conserved origins and life cycles

Science Immunology, Journal Year: 2022, Volume and Issue: 7(67)

Published: Jan. 7, 2022

Resident macrophages orchestrate homeostatic, inflammatory, and reparative activities. It is appreciated that different tissues instruct specialized macrophage functions. However, individual contain heterogeneous subpopulations, how these subpopulations are related unclear. We asked whether common transcriptional functional elements could reveal an underlying framework across tissues. Using single-cell RNA sequencing random forest modeling, we observed four genes predict three subsets were present in murine heart, liver, lung, kidney, brain. Parabiotic genetic fate mapping studies revealed core markers predicted unique life cycles 17 TLF+ (expressing TIMD4 and/or LYVE1 FOLR2) maintained through self-renewal with minimal monocyte input; CCR2+ (TIMD4−LYVE1−FOLR2−) almost entirely replaced by monocytes, MHC-IIhi (TIMD4−LYVE1−FOLR2−CCR2−), while receiving modest contribution, not continually replaced. Rather, monocyte-derived contributed to the resident population until they reached a defined upper limit after which did outcompete pre-existing macrophages. Developmentally, first emerge yolk sac early fetal organs. Fate mouse human indicated originated from both precursors. Furthermore, most transcriptionally conserved subset between mice humans, despite organ- species-specific differences. Here, define existence of based on cycle properties gene signatures provide starting point understand tissue heterogeneity.

Language: Английский

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Inflammatory Cytokines and Chemokines as Therapeutic Targets in Heart Failure

Cardiovascular Drugs and Therapy, Journal Year: 2020, Volume and Issue: 34(6), P. 849 - 863

Published: Sept. 9, 2020

Language: Английский

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Role of Cardiac Macrophages on Cardiac Inflammation, Fibrosis and Tissue Repair

Cells, Journal Year: 2020, Volume and Issue: 10(1), P. 51 - 51

Published: Dec. 31, 2020

The immune system plays a pivotal role in the initiation, development and resolution of inflammation following insult or damage to organs. heart is vital organ which supplies nutrients oxygen all parts body. Heart failure (HF) has been conventionally described as disease associated with cardiac tissue caused by systemic inflammation, arrhythmia conduction defects. Cardiac subsequent orchestrated infiltration activation various cells including neutrophils, monocytes, macrophages, eosinophils, mast cells, natural killer T B into myocardium. After injury, monocytes tissue-resident macrophages undergo marked phenotypic functional changes, function key regulators repair, regeneration fibrosis. Disturbance resident macrophage functions such uncontrolled production inflammatory cytokines, growth factors inefficient generation an anti-inflammatory response unsuccessful communication between epithelial endothelial fibroblasts can lead aberrant persistent HF. Therefore, this review, we discuss on

Language: Английский

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Single-cell transcriptomics reveals cell-type-specific diversification in human heart failure

Nature Cardiovascular Research, Journal Year: 2022, Volume and Issue: 1(3), P. 263 - 280

Published: March 16, 2022

Heart failure represents a major cause of morbidity and mortality worldwide. Single-cell transcriptomics have revolutionized our understanding cell composition associated gene expression. Through integrated analysis single-cell single-nucleus RNA-sequencing data generated from 27 healthy donors 18 individuals with dilated cardiomyopathy, here we define the failing human heart. We identify cell-specific transcriptional signatures age heart reveal emergence disease-associated states. Notably, cardiomyocytes converge toward common states, whereas fibroblasts myeloid cells undergo dramatic diversification. Endothelial pericytes display global shifts without changes in complexity. Collectively, findings provide comprehensive cellular transcriptomic landscape failure, type-specific programs states establish valuable resource for investigation failure.

Language: Английский

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