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WIREs Syst Biol Med
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The macrophage and its role in inflammation and tissue repair: mathematical and systems biology approaches

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Macrophages are central to the inflammatory response and its ability to resolve effectively. They are complex cells that adopt a range of subtypes depending on the tissue type and stimulus that they find themselves under. This flexibility allows them to play multiple, sometimes opposing, roles in inflammation and tissue repair. Their central role in the inflammatory process is reflected in macrophage dysfunction being implicated in chronic inflammation and poorly healing wounds. In this study, we discuss recent attempts to model mathematically and computationally the macrophage and how it partakes in the complex processes of inflammation and tissue repair. There are increasing data describing the variety of macrophage phenotypes and their underlying transcriptional programs. Dynamic mathematical and computational models are an ideal way to test biological hypotheses against experimental data and could aid in understanding this multi‐functional cell and its potential role as an attractive therapeutic target for inflammatory conditions and tissue repair. WIREs Syst Biol Med 2016, 8:87–99. doi: 10.1002/wsbm.1320 This article is categorized under: Biological Mechanisms > Cell Fates Models of Systems Properties and Processes > Cellular Models Models of Systems Properties and Processes > Mechanistic Models
Macrophage role in inflammation and tissue repair. Upon stimulus monocytes and resident macrophages activate. They remove tissue debris and produce inflammatory signals that promote the inflammatory response. Macrophages produce a wide array of cytokines, chemokines, and growth factors that promote inflammation, its regulation, and the successful restoration of tissue. They also participate in the regulation of inflammation by removing apoptotic neutrophils, an important process in turning the inflammatory process to one of tissue replacement and remodeling, apoptotic neutrophils that are not removed can undergo necrosis, spilling their toxic content and perpetuating the inflammatory response.
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Macrophages play a key role in inflammation and tissue repair tailoring their behavior to signals from their environment. Traditionally, two main macrophage phenotypes have been identified: M1 (classically activated) that are pro‐inflammatory in nature, promoting the killing of pathogens and driving the inflammatory response and M2 (alternatively activated) that are thought to upregulate anti‐inflammatory cytokine secretion and activate downstream tissue repair. The understanding of macrophage heterogeneity is changing rapidly, driven by gene expression data that displays no single marker of phenotype; it is now thought that macrophages display shades of activation, suggesting there may be a continuum of phenotypes. While the M1/M2 paradigm can provide a simplified description that can be used to aid in deciphering the role of macrophages in health and disease classification of macrophage heterogeneity is only likely to expand. Source: Mosser and Edwards.
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Biological Mechanisms > Cell Fates
Models of Systems Properties and Processes > Mechanistic Models
Models of Systems Properties and Processes > Cellular Models

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