title: Molecular and epigenetic basis of macrophage polarized activation.
abstract: Macrophages are unique cells for origin, heterogeneity and plasticity. At steady state most of macrophages are derived from fetal sources and maintained in adulthood through self-renewing. Despite sharing common progenitors, a remarkable heterogeneity characterized tissue-resident macrophages indicating that local signals educate them to express organ-specific functions. Macrophages are extremely plastic: chromatin landscape and transcriptional programs can be dynamically re-shaped in response to microenvironmental changes. Owing to their ductility, macrophages are crucial orchestrators of both initiation and resolution of immune responses and key supporters of tissue development and functions in homeostatic and pathological conditions. Herein, we describe current understanding of heterogeneity and plasticity of macrophages using the M1-M2 dichotomy as operationally useful simplification of polarized activation. We focused on the complex network of signaling cascades, metabolic pathways, transcription factors, and epigenetic changes that control macrophage activation. In particular, this network was addressed in sepsis, as a paradigm of a pathological condition determining dynamic macrophage reprogramming.
authors.affiliation: Department of Pharmaceutical Sciences, Università del Piemonte Orientale "Amedeo Avogadro", via Bovio 6, Novara, Italy. Electronic address: chiara.porta@uniupo.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Porta
authors.affiliation: Department of Pharmaceutical Sciences, Università del Piemonte Orientale "Amedeo Avogadro", via Bovio 6, Novara, Italy. Electronic address: elena.riboldi@uniupo.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Riboldi
authors.affiliation: Department of Pharmaceutical Sciences, Università del Piemonte Orientale "Amedeo Avogadro", via Bovio 6, Novara, Italy. Electronic address: alessandro.ippolito@uniupo.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ippolito
authors.affiliation: Department of Pharmaceutical Sciences, Università del Piemonte Orientale "Amedeo Avogadro", via Bovio 6, Novara, Italy; Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, Milan 20089, Italy. Electronic address: antonio.sica@uniupo.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Sica
mesh_terms: D000818:Animals; D044127:Epigenesis, Genetic; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008262:Macrophage Activation; D009369:Neoplasms / Q000276:immunology; D009765:Obesity / Q000276:immunology; D014945:Wound Healing
keywords: Activation; Epigenetic; Gene expression; Macrophage; Metabolism; Plasticity