Macrophage heterogeneity in liver injury and fibrosis.
By F. Tacke, H. Zimmermann. Journal of Hepatology, 2014
995 citations recorded by the source corpus.
Hepatic macrophages are central in the pathogenesis of chronic liver injury and have been proposed as potential targets in combatting fibrosis. Recent experimental studies in animal models revealed that hepatic macrophages are a remarkably heterogeneous population of immune cells that fulfill diverse functions in homeostasis, disease progression, and regression from injury. These range from clearance of pathogens or cellular debris and maintenance of immunological tolerance in steady state conditions; central roles in initiating and perpetuating inflammation in response to injury; promoting liver fibrosis via activating hepatic stellate cells in chronic liver damage; and, finally, resolution of inflammation and fibrosis by degradation of extracellular matrix and release of anti-inflammatory cytokines. Cellular heterogeneity in the liver is partly explained by the origin of macrophages. Hepatic macrophages can either arise from circulating monocytes, which are recruited to the injured liver via chemokine signals, or from self-renewing embryo-derived local macrophages, termed Kupffer cells. Kupffer cells appear essential for sensing tissue injury and initiating inflammatory responses, while infiltrating Ly-6C(+) monocyte-derived macrophages are linked to chronic inflammation and fibrogenesis. In addition, proliferation of local or recruited macrophages may possibly further contribute to their accumulation in injured liver. During fibrosis regression, monocyte-derived cells differentiate into Ly-6C (Ly6C, Gr1) low expressing 'restorative' macrophages and promote resolution from injury. Understanding the mechanisms that regulate hepatic macrophage heterogeneity, either by monocyte subset recruitment, by promoting restorative macrophage polarization or by impacting distinctive macrophage effector functions, may help to develop novel macrophage subset-targeted therapies for liver injury and fibrosis.
View Paper: https://www.semanticscholar.org/paper/ac20e8b29fed7cd490ba43762eafc2b8d9bfdb34
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- D. Schuppan
- M. Pinzani
- Natascha Roehlen
- Seyed-Alireza Esmaeili
- A. Shapouri-Moghaddam
- Amirhossein Sahebkar
- M. Taghadosi
- D. Hirayama
Citations in the corpus
- Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages (2018, unknown): “Our results show that I3A and TA both inhibit BMDM migration toward MCP-1 in a dose-dependent manner; however, the mechanism for this inhibition remains to be elucidated.”
- Macrophage plasticity, polarization, and function in health and disease (2018, background): “…in the recovery phase of fibrosis by inducing ECM degradation, phagocytosis apoptotic myofibroblasts, and dampening the immune response that contributes to tissue injury (Braga et al., 2015; Sica et al., 2014; Tacke & Zimmermann, 2014;Wick et al., 2010; Wynn & Ramalingam, 2012; Xu et al., 2012).”
- Hepatic stellate cells as key target in liver fibrosis (2017, unknown): “paracrine regulation of HSC activation [41,58].”
- Hepatic fibrosis: Concept to treatment. (2015, background): “The fractalkine receptor CX3CR1 may be a key pathway mediating this switch, because its greater abundance is associated with a pro-resolution Ly6C macrophage phenotype [14].”
- Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives (2020, background): “Distinct macrophage subpopulations on the other hand participate in fibrosis resolution due to expression of matrix-metalloproteinases (MMPs) [15,16].”
- The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis (2017, background): “Kupffer cells are seeded alongside sinusoidal endothelial cells and are important scavengers that constantly clear gutderived pathogens from the blood [40].”