Iron scavenging and myeloid cell polarization

As a main source of erythrocyte degradation products, the process of hemolysis is a key determinant in skewing proinflammatory signatures in myeloid cells.Hemolytic products such as heme and iron can elicit proinflammatory effects, activating endothelial tissues and innate immunity.Iron plays an important role in myeloid cell polarization by altering cellular signaling and metabolism, while also affecting chromatin modifications.The interplay between iron and myeloid cells can influence the progression of several diseases, including sickle cell disease, multiple sclerosis (MS), and cancers.Iron-loaded myeloid cells are spatially organized, often surrounding lesions in MS and tumor masses. Myeloid cell polarization is linked to the iron scavenging and storage functions of these cells in a tissue-dependent manner. New studies are advancing our knowledge of iron as a modulator of immune functions, cell metabolism, and myeloid cell polarization into proinflammatory or anti-inflammatory functions. Considering the significance of myeloid cells at steady state and under disease conditions, it is important to understand the different functions and effects of iron-loaded myeloid cells. Iron-associated myeloid cell functions can be disease-dependent and the cells may exhibit polarizing functions during inflammation. Myeloid cells that populate all human organs and blood are a versatile class of innate immune cells. They are crucial for sensing and regulating processes as diverse as tissue homeostasis and inflammation and are frequently characterized by their roles in either regulating or promoting inflammation. Recent studies in cultured cells and mouse models highlight the role of iron in skewing the functional properties of myeloid cells in tissue damage and repair. Here, we review certain emerging concepts on how iron influences and determines myeloid cell polarization in the context of its uptake, storage, and metabolism, including in conditions such as multiple sclerosis (MS), sickle cell disease, and tumors. Myeloid cells that populate all human organs and blood are a versatile class of innate immune cells. They are crucial for sensing and regulating processes as diverse as tissue homeostasis and inflammation and are frequently characterized by their roles in either regulating or promoting inflammation. Recent studies in cultured cells and mouse models highlight the role of iron in skewing the functional properties of myeloid cells in tissue damage and repair.