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Emerging role of macrophages in non-infectious diseases: An update

Journal

BIOMEDICINE & PHARMACOTHERAPY
Volume 161, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2023.114426

Keywords

Macrophages; Monocytes; Non-infectious diseases; Atherosclerosis; Asthma; Rheumatoid arthritis (RA); Inflammatory bowel disease (IBD); Breast Cancer

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In the past three decades, research studies on animal models have provided a wealth of evidence showing the central role of macrophages in diseases, especially in non-infectious diseases, where they are often referred to as double-edged swords. Macrophages, as the most versatile immunocytes, play a key role in both health and diseases. The conventional paradigms of macrophages, such as the M1/M2 dichotomy, have been challenged by various experimental models, revealing a complex characterization of macrophages in disease immunology. In human diseases, macrophages demonstrate a complex web of mechanisms, with pro-inflammatory roles (mediated by cytokines such as IL-1, IL-6, IL-12, IL-23, and tumor necrosis factor) and anti-inflammatory roles (including CCl-17, CCl-22, CCL-2, transforming growth factor (TGF), and interleukin-10), which are involved in wound healing and pathogen-suppression. The conventional division of macrophages into M1 and M2 is based on their opposing functions, with M1 being involved in tissue damage and pro-inflammatory roles, and M2 promoting cell proliferation and inflammation resolution. These pathways mutually down-regulate each other in diseases through a variety of enzymatic and cytokine mediators.
In the past three decades, a huge body of evidence through various research studies conducted on animal models, has demonstrated that the macrophages are centralized of all the leukocytes involved in diseases and, particu-larly, their role in non-infectious diseases has been studied extensively for which they have also been referred to as the double-edged swords. The most versatile of all immunocytes, macrophages play a key role in health and diseases. Various experimental models have demonstrated the conventional paradigms such as the M1/M2 di-chotomy, which is not as obvious and presents a complex characterization of the macrophages in the disease immunology. In human diseases, this M1-M2 continuum shows a complex web of mechanisms, which are majorly divided into the pro-inflammatory roles (derived mainly by the cytokines: IL-1, IL-6, IL-12, IL-23, and tumor necrosis factor) and anti-inflammatory roles (CCl-17, CCl-22, CCL-2, transforming growth factor (TGF), and interleukin-10), which are involved in the wound healing and pathogen-suppression. The conventional division of these macrophages as M1 and M2 is derived from the opposing functions of these macrophages; where M1 is involved in the tissue damage and pro-inflammatory roles and M2 promotes cell proliferation and the resolution of inflammation. Both these pathways down-regulate each other in diseases through a plethora of enzymatic and cytokine mediators.

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