Neutrophils direct preexisting matrix to initiate repair in damaged tissues

Fischer, Adrian; Wannemacher, Juliane; Christ, Simon; Koopmans, Tim; Kadri, Safwen; Zhao, Jiakuan; Gouda, Mahesh; Ye, Haifeng; Mück-Häusl, Martin; Krenn, Peter W.; Machens, Hans‐Günther; Fässler, Reinhard; Neumann, Philipp‐Alexander; Hauck, Stefanie M.; Rinkevich, Yuval

doi:10.1038/s41590-022-01166-6

Cited by 55 publications

(41 citation statements)

References 44 publications

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“…Neutrophils can respond and adapt to the migrated circumstance with transcriptional modification (6,76,77). Treg/IL-10 educated neutrophils can become IL-10-producing and later apoptotic, assisting repair of damaged tissue by transferring preexisting matrix and fueling repair activities of other immune cells, such as monocytes, macrophages, and type 3 innate lymphoid cells (53, 76,78,79). Taken together, neutrophils are not limited to regulating inflammation in inflamed sites, but can also act as pioneers of systemic immune regulators.…”

Section: Programed Neutrophil Apoptosis and Initiation Of Resolutionmentioning

confidence: 99%

Emerging roles of neutrophils in immune homeostasis

Lee¹,

Lee²,

Bae³

2022

BMB Rep

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Neutrophils, the most abundant innate immune cells, play essential roles in the innate immune system. As key innate immune cells, neutrophils detect intrusion of pathogens and initiate immune cascades with their functions; swarming (arresting), cytokine production, degranulation, phagocytosis, and projection of neutrophil extracellular trap. Because of their short lifespan and consumption during immune response, neutrophils need to be generated consistently, and generation of newborn neutrophils (granulopoiesis) should fulfill the environmental/systemic demands for training in cases of infection. Accumulating evidence suggests that neutrophils also play important roles in the regulation of adaptive immunity. Neutrophil-mediated immune responses end with apoptosis of the cells, and proper phagocytosis of the apoptotic body (efferocytosis) is crucial for initial and post resolution by producing tolerogenic innate/adaptive immune cells. However, inflammatory cues can impair these cascades, resulting in systemic immune activation; necrotic/pyroptotic neutrophil bodies can aggravate the excessive inflammation, increasing inflammatory macrophage and dendritic cell activation and subsequent TH1/TH17 responses contributing to the regulation of the pathogenesis of autoimmune disease. In this review, we briefly introduce recent studies of neutrophil function as players of immune response. [BMB Reports 2022; 55(10): 473-480]

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Section: Programed Neutrophil Apoptosis and Initiation Of Resolutionmentioning

confidence: 99%

Emerging roles of neutrophils in immune homeostasis

Lee¹,

Lee²,

Bae³

2022

BMB Rep

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“…The overall neutrophil responses are tightly controlled by various transcription factors, as shown in a zymosan air pouch model, including RUNX1 and KLF6, being implicated in both neutrophil maturation and recruitment, while RFX2 and RELB are implicated in neutrophil survival; in this experimental setting, RELB, IRF5 and JUNB regulate neutrophil activation and effector functions [ 253 ]. An interesting function has been attributed to neutrophils in injury settings; herein, they transport matrix components to a wounded site, leading to scar formation in a kindlin-3-integrin-activation-dependent manner in which heat shock proteins induce integrin heterodimerization, indicating that an activated, supposedly pro-inflammatory phenotype can be functionally rather diverse, and even take on a profile comparable to reparative M2 macrophage features [ 254 ]. Phenotypic modulation of neutrophil responses is due to various activation/deactivation mechanisms.…”

Section: Regulatory Aspects Of Damps Pamps Microenvironments and Cell...mentioning

confidence: 99%

Immune Cell Plasticity in Inflammation: Insights into Description and Regulation of Immune Cell Phenotypes

Margraf

Perretti

2022

Cells

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Inflammation is a life-saving immune reaction occurring in response to invading pathogens. Nonetheless, inflammation can also occur in an uncontrolled, unrestricted manner, leading to chronic disease and organ damage. Mechanisms triggering an inflammatory response, hindering such a response, or leading to its resolution are well-studied but so far insufficiently elucidated with regard to precise therapeutic interventions. Notably, as an immune reaction evolves, requirements and environments for immune cells change, and thus cellular phenotypes adapt and shift, leading to the appearance of distinct cellular subpopulations with new functional features. In this article, we aim to highlight properties of, and overarching regulatory factors involved in, the occurrence of immune cell phenotypes with a special focus on neutrophils, macrophages and platelets. Additionally, we point out implications for both diagnostics and therapeutics in inflammation research.

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“…In experimental acute sterile lung injury in mice, alveolar neutrophils acquire the ability to take up and degrade extracellular DNA fragments and allow optimal organ repair only when they are exposed to an inflammatory environment [ 155 ]. Furthermore, neutrophils are said to be able to transport matrix from normal to damaged organs to promote wound healing [ 156 ]. Consequently, the development of treatments targeting neutrophils in aseptic inflammation must also consider their anti-inflammatory and tissue repair functions.…”

Section: Potential Therapeutics Targeting Netsmentioning

confidence: 99%

Neutrophils and Neutrophil Extracellular Traps in Cardiovascular Disease: An Overview and Potential Therapeutic Approaches

Shirakawa

Sano

2022

Biomedicines

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Recent advances in pharmacotherapy have markedly improved the prognosis of cardiovascular disease (CVD) but have not completely conquered it. Therapies targeting the NOD-like receptor family pyrin domain containing 3 inflammasome and its downstream cytokines have proven effective in the secondary prevention of cardiovascular events, suggesting that inflammation is a target for treating residual risk in CVD. Neutrophil-induced inflammation has long been recognized as important in the pathogenesis of CVD. Circadian rhythm-related and disease-specific microenvironment changes give rise to neutrophil diversity. Neutrophils are primed by various stimuli, such as chemokines, cytokines, and damage-related molecular patterns, and the activated neutrophils contribute to the inflammatory response in CVD through degranulation, phagocytosis, reactive oxygen species generation, and the release of neutrophil extracellular traps (NETs). In particular, NETs promote immunothrombosis through the interaction with vascular endothelial cells and platelets and are implicated in the development of various types of CVD, such as acute coronary syndrome, deep vein thrombosis, and heart failure. NETs are promising candidates for anti-inflammatory therapy in CVD, and their efficacy has already been demonstrated in various animal models of the disease; however, they have yet to be clinically applied in humans. This narrative review discusses the diversity and complexity of neutrophils in the trajectory of CVD, the therapeutic potential of targeting NETs, and the related clinical issues.

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Neutrophils direct preexisting matrix to initiate repair in damaged tissues

Cited by 55 publications

References 44 publications

Emerging roles of neutrophils in immune homeostasis

Emerging roles of neutrophils in immune homeostasis

Immune Cell Plasticity in Inflammation: Insights into Description and Regulation of Immune Cell Phenotypes

Neutrophils and Neutrophil Extracellular Traps in Cardiovascular Disease: An Overview and Potential Therapeutic Approaches

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