title: Iron levels in polarized macrophages: regulation of immunity and autoimmunity.
abstract: Although the hallmark of autoimmune diseases remains the generation of autoantigen-specific lynfocytic cell response, growing evidence is showing a key role for macrophages in a number of autoimmune diseases. Macrophages are characterized by phenotypical and functional heterogeneity. Different immunological signals, coming from systemic blood circulation or from microenvironment, polarize macrophages to classical (M1) or alternative (M2) phenotypes. Iron accumulation in M1 macrophages is a well known bacteriostatic mechanism and one of the mechanisms at the basis of anemia associated to chronic inflammation. Moreover, some recent data suggest that iron accumulation in macrophages can directly activate macrophages to pro-inflammatory M1 phenotype, highlighting a putative role of macrophage iron retention in the pathogenesis of chronic inflammatory and autoimmune diseases. Conversely, iron content is low in M2 macrophages, principally due to increased iron release, and increased availability of iron in the extracellular milieu supported by M2 macrophages could influence the growth rate of adjacent cell and thus play an important role in tumor growth and tissue remodeling. In this review we summarize the molecular mechanisms sustaining differential iron metabolism in polarized macrophages, discuss the relevance of this metabolic signature in chronic inflammatory and autoimmune diseases, and finally focus on potential therapeutic implications rising from a better understanding of underlying molecular mechanisms.
authors.affiliation: Department of Human Morphology and Biomedical Sciences Città Studi, University of Milan, Milan, Italy. stefania.recalcati@unimi.it
authors.forename: Stefania
authors.initials: S
authors.lastname: Recalcati
authors.forename: Massimo
authors.initials: M
authors.lastname: Locati
authors.forename: Elena
authors.initials: E
authors.lastname: Gammella
authors.forename: Pietro
authors.initials: P
authors.lastname: Invernizzi
authors.forename: Gaetano
authors.initials: G
authors.lastname: Cairo
mesh_terms: D000818:Animals; D015551:Autoimmunity; D002454:Cell Differentiation; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D006801:Humans; D056747:Immunomodulation; D018836:Inflammation Mediators / Q000378:metabolism; D007501:Iron / Q000276:immunology / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D007501:Iron