Macrophages and fibrosis: How resident and infiltrating mononuclear phagocytes orchestrate all phases of tissue injury and repair

• Published in: Biochimica et biophysica acta Vol. 1832; no. 7; pp. 989 - 997
• Main Authors: Lech, Maciej, Anders, Hans-Joachim
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2013
• Subjects: Fibrosis; Humans; Immunity; Inflammation; Macrophages - metabolism; Monocytes - metabolism; Polarization; Regeneration; Transforming Growth Factor beta1 - metabolism; Wound Healing; Regeneration; Polarization; Inflammation; Wound healing; Immunity; Fibrosis
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2012.12.001

Certain macrophage phenotypes contribute to tissue fibrosis, but why? Tissues host resident mononuclear phagocytes for their support to maintain homeostasis. Upon injury the changing tissue microenvironment alters their phenotype and primes infiltrating monocytes toward pro-inflammatory macrophages. Several mechanisms contribute to their deactivation and macrophage priming toward anti-inflammatory and pro-regenerative macrophages that produce multiple cytokines that display immunosuppressive as well as pro-regeneratory effects, such as IL-10 and TGF-beta1. Insufficient parenchymal repair creates a tissue microenvironment that becomes dominated by multiple growth factors that promote the pro-fibrotic macrophage phenotype that itself produces large amounts of such growth factors that further support fibrogenesis. However, the contribution of resident mononuclear phagocytes to physiological extracellular matrix turnover implies also their fibrolytic effects in the late stage of tissue scaring. Fibrolytic macrophages break down fibrous tissue, but their phenotypic characteristics remain to be described in more detail. Together, macrophages contribute to tissue fibrosis because the changing tissue environments prime them to assist and orchestrate all phases of tissue injury and repair. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease. ► Fibrosis was selected throughout evolution because of its life saving benefits. ► Macrophages contribute to fibrosis because they contribute to all phases of tissue injury and repair. ► Macrophages not only support fibrogenesis, but they also support fibrolysis. ► Suppressing sterile tissue inflammation and promoting tissue regeneration are the best way to prevent tissue fibrosis.