Abstract
Control of homeostasis and rapid response to tissue damage in the liver is orchestrated by crosstalk between resident and infiltrating inflammatory cells. A crucial role for myeloid cells during hepatic injury and repair has emerged where resident Kupffer cells, circulating monocytes, macrophages, dendritic cells and neutrophils control local tissue inflammation and regenerative function to maintain tissue architecture. Studies in humans and rodents have revealed a heterogeneous population of myeloid cells that respond to the local environment by either promoting regeneration or driving the inflammatory processes that can lead to hepatitis, fibrogenesis, and the development of cirrhosis and malignancy. Such plasticity of myeloid cell responses presents unique challenges for therapeutic intervention strategies and a greater understanding of the underlying mechanisms is needed. Here we review the role of myeloid cells in the establishment and progression of liver disease and highlight key pathways that have become the focus for current and future therapeutic strategies.
Highlights
Myeloid cells arise from the common myeloid precursor and give rise to monocytes, dendritic cells and macrophages, and granulocytes
The liver contains a population of self-renewing resident macrophages, termed Kupffer cells (KC), derived from yolk sac-derived progenitor cells [8, 9] or hematopoietic stem cells
Circulating monocytes are actively recruited to the liver, guided by adhesion molecules and chemokine gradients generated at the sinusoidal endothelial interface
Summary
Adams DH (2019) The Role of Myeloid-Derived Cells in the Progression of Liver Disease. Studies in humans and rodents have revealed a heterogeneous population of myeloid cells that respond to the local environment by either promoting regeneration or driving the inflammatory processes that can lead to hepatitis, fibrogenesis, and the development of cirrhosis and malignancy. Such plasticity of myeloid cell responses presents unique challenges for therapeutic intervention strategies and a greater understanding of the underlying mechanisms is needed. We review the role of myeloid cells in the establishment and progression of liver disease and highlight key pathways that have become the focus for current and future therapeutic strategies
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