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Macrophage Plasticity in Skin Fibrosis

  • Melanie Rodrigues
  • Clark A. Bonham
Chapter
Part of the Molecular and Translational Medicine book series (MOLEMED)

Abstract

Macrophages are highly plastic cells of myeloid origin which are causative for several diseases. In the past two decades, macrophages have been studied for their involvement in various forms of skin fibrosis. This includes hypertrophic scarring following burn, radiation and trauma injuries, rare diseases such as scleroderma, and the foreign body response evoked in response to subcutaneously implanted biomaterials. The extent of fibrosis can be correlated with alterations in macrophage number and a deviation in their spatial and temporal function. However, identifying the predominant macrophage function at a given time and determining aberrations have been difficult due to the numerous characteristics acquired by these unique cells, also referred to as macrophage heterogeneity. These functions include but are not limited to phagocytosis, production of reactive oxygen species and inflammatory cytokines, deposition of extracellular matrix, lysis of extracellular matrix, production of regenerative cytokines, blood vessel fusion, and macrophage self-fusion to form multinucleated giant cells. By performing these functions, macrophages exert influences on other stromal cells such as fibroblasts and endothelial cells and immune cells such as T-lymphocytes and the ECM itself. Some of the influences are desirable and necessary for healing, which implies that depletion of macrophages cannot be a simple solution to preventing fibrosis. Here, we will address changing macrophage phenotypes in skin fibrosis and the influence that macrophage ontogeny, epigenetic factors, and the microenvironment exert on these phenotypes. A more thorough understanding will aid in the discovery of unique biomarkers for fibrosis and in the development of targeted therapies.

Keywords

Macrophage heterogeneity Macrophage plasticity Skin fibrosis Hypertrophic scarring Scleroderma Foreign body reaction 

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of SurgeryStanford University School of MedicineStanfordUSA

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