Macrophage Polarization

Annual Review of Physiology, Journal Year: 2016, Volume and Issue: 79(1), P. 541 - 566

Published: Nov. 4, 2016

Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as are sufficiently plastic integrate multiple signals, such those from microbes, damaged tissues, the normal tissue environment. Three broad pathways control polarization: epigenetic cell survival that prolong or shorten macrophage development viability, microenvironment, extrinsic factors, microbial products cytokines released inflammation. A plethora of advances provided framework for rationally purifying, describing, manipulating polarization. Here, I assess current state knowledge about enumerate major questions regulate physiology tissues.

Language: Английский

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Fibrosis: from mechanisms to medicines

Nature, Journal Year: 2020, Volume and Issue: 587(7835), P. 555 - 566

Published: Nov. 25, 2020

Language: Английский

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Inflammation and metabolism in tissue repair and regeneration

Science, Journal Year: 2017, Volume and Issue: 356(6342), P. 1026 - 1030

Published: June 9, 2017

Tissue repair after injury is a complex, metabolically demanding process. Depending on the tissue’s regenerative capacity and quality of inflammatory response, outcome generally imperfect, with some degree fibrosis, which defined by aberrant accumulation collagenous connective tissue. Inflammatory cells multitask at wound site facilitating debridement producing chemokines, metabolites, growth factors. If this well-orchestrated response becomes dysregulated, can become chronic or progressively fibrotic, both outcomes impairing tissue function, ultimately lead to organ failure death. Here we review current understanding role inflammation cell metabolism in tissue-regenerative responses, highlight emerging concepts that may expand therapeutic perspectives, briefly discuss where important knowledge gaps remain.

Language: Английский

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Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span

The Journal of Experimental Medicine, Journal Year: 2017, Volume and Issue: 214(8), P. 2387 - 2404

Published: July 10, 2017

Little is known about the relative importance of monocyte and tissue-resident macrophages in development lung fibrosis. We show that specific genetic deletion monocyte-derived alveolar after their recruitment to ameliorated fibrosis, whereas did not contribute Using transcriptomic profiling flow-sorted cells, we found macrophage differentiation unfolds continuously over course fibrosis its resolution. During fibrotic phase, differ significantly from expression profibrotic genes. A population persisted for one year resolution where they became increasingly similar macrophages. Human homologues genes expressed by mouse during were up-regulated human compared with normal lungs. Our findings suggest selectively targeting within may ameliorate without adverse consequences associated global or depletion.

Language: Английский

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Anti–spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection

JCI Insight, Journal Year: 2019, Volume and Issue: 4(4)

Published: Feb. 20, 2019

Newly emerging viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle Eastern CoVs (MERS-CoV), and H7N9, cause fatal lung injury (ALI) by driving hypercytokinemia aggressive inflammation through mechanisms that remain elusive. In SARS-CoV/macaque models, we determined anti–spike IgG (S-IgG), in productively infected lungs, causes ALI skewing inflammation-resolving response. Alveolar macrophages underwent functional polarization acutely macaques, demonstrating simultaneously both proinflammatory wound-healing characteristics. The presence of S-IgG prior to viral clearance, however, abrogated responses promoted MCP1 IL-8 production monocyte/macrophage recruitment accumulation. Critically, patients who eventually died SARS (hereafter referred deceased patients) displayed similarly accumulated pulmonary proinflammatory, absence macrophages, faster neutralizing antibody responses. Their sera enhanced SARS-CoV–induced human monocyte–derived whereas blockade FcγR reduced effects. Our findings reveal a mechanism responsible for virus-mediated ALI, define pathological consequence specific response, provide potential target treatment SARS-CoV or other injury.

Language: Английский

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Type 2 immunity in tissue repair and fibrosis

Nature reviews. Immunology, Journal Year: 2017, Volume and Issue: 18(1), P. 62 - 76

Published: Aug. 30, 2017

Language: Английский

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The Neutrophil’s Role During Health and Disease

Physiological Reviews, Journal Year: 2019, Volume and Issue: 99(2), P. 1223 - 1248

Published: Feb. 13, 2019

Neutrophils have always been considered as uncomplicated front-line troopers of the innate immune system equipped with limited proinflammatory duties. Yet recently, role neutrophil has undergoing a rejuvenation sorts. are now complex cells capable significant array specialized functions, and an effector response, they able to regulate many processes such acute injury repair, cancer, autoimmunity, chronic inflammatory processes. Furthermore, evidence exists indicate that neutrophils also contribute adaptive immunity by aiding development specific responses or guiding subsequent response. With this revived interest in their novel it is prudent review what currently known about and, even more importantly, understand information lacking. We discuss essential features neutrophil, from its origins, lifespan, subsets, margination sequestration death neutrophil. highlight recruitment both infected injured tissues outline differences between different tissues. Finally, we examine how use mechanisms either bolster protective negatively cause pathological outcomes at locations.

Language: Английский

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Transforming growth factor–β in tissue fibrosis

The Journal of Experimental Medicine, Journal Year: 2020, Volume and Issue: 217(3)

Published: Feb. 20, 2020

TGF-β is extensively implicated in the pathogenesis of fibrosis. In fibrotic lesions, spatially restricted generation bioactive from latent stores requires cooperation proteases, integrins, and specialized extracellular matrix molecules. Although fibroblasts are major targets TGF-β, some fibrogenic actions may reflect activation other cell types, including macrophages, epithelial cells, vascular cells. TGF-β–driven fibrosis mediated through Smad-dependent or non-Smad pathways modulated by coreceptors interacting networks. This review discusses role fibrosis, highlighting mechanisms signaling, cellular actions, challenges therapeutic translation.

Language: Английский

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Macrophages in immunoregulation and therapeutics

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 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.

Language: Английский

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Phagocytosis: An Immunobiologic Process

Immunity, Journal Year: 2016, Volume and Issue: 44(3), P. 463 - 475

Published: March 1, 2016

Language: Английский

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