Histiocytes: Multifaceted Regulators of Health and Disease

The mononuclear phagocyte system encompasses macrophages, dendritic cells (DCs), and monocytes. Tissue-resident macrophages and dendritic cells arise during embryogenesis and are replenished either through self-renewal or by monocytes during inflammation. Tissue macrophages and DCs are indistinguishable by light microscopy, thus "histiocyte" is often used in diagnostic pathology to denote both cell types. Macrophages and DCs play essential roles in immune surveillance, inflammation, antigen presentation, and tissue repair and homeostasis. Functions essential to these roles include internalization of foreign and host-derived materials via phagocytosis, endocytosis, and pinocytosis; coordination of immune and non-immune cells via release of cytokines, chemokines, and growth factors; and activation of T cell response via antigen presentation. Their remarkable functional plasticity is governed by ontogeny, tissue of residence, and exquisite sensitivity to a wide variety of signals from pathogens, damaged and recovering tissues, extracellular matrix, and other immune cells.