Implications of macrophage polarization in autoimmunity

Abstract

SummaryMacrophages are extremely heterogeneous and plastic cells with an important role not only in physiological conditions, but also during inflammation (both for initiation and resolution). In the early 1990s, two different phenotypes of macrophages were described: one of them called classically activated (or inflammatory) macrophages (M1) and the other alternatively activated (or wound-healing) macrophages (M2). Currently, it is known that functional polarization of macrophages into only two groups is an over-simplified description of macrophage heterogeneity and plasticity; indeed, it is necessary to consider a continuum of functional states. Overall, the current available data indicate that macrophage polarization is a multifactorial process in which a huge number of factors can be involved producing different activation scenarios. Once a macrophage adopts a phenotype, it still retains the ability to continue changing in response to new environmental influences. The reversibility of polarization has a critical therapeutic value, especially in diseases in which an M1/M2 imbalance plays a pathogenic role. In this review, we assess the high plasticity of macrophages and their potential to be exploited to reduce chronic/detrimental inflammation. On the whole, the evidence detailed in this review underscores macrophage polarization as a target of interest for immunotherapy.

The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions

“…Overwhelming evidence has associated chronic inflammation with various pathological conditions and their potential causes, including atherosclerosis, cardiovascular events, cancer, autoimmune diseases, metabolic disorders, neurological diseases, and aging (Johnston et al 1987;Gisterå and Hansson 2017;Tabas and Lichtman 2017;de Vries and Quax 2018;Gomez et al 2018;Aday and Ridker 2019;Bercovici et al 2019;Di Benedetto et al 2019;Guner and Kim 2019;Horwitz et al 2019;O'Rourke et al 2019;Othman et al 2019;Trott and Fadel 2019). Many investigations have focused on the major role of macrophages in such contexts and mechanisms for their proinflammatory activation (Murray and Wynn 2011;Wynn and Vannella 2016;Gisterå and Hansson 2017;Tabas and Lichtman 2017;Decano and Aikawa 2018;Funes et al 2018;Swirski and Nahrendorf 2018;O'Rourke et al 2019). Various signal-transduction pathways participate in macrophage activation, which are often regulated by PTMs such as phosphorylation and acetylation (Tietzel and Mosser 2002;Park et al 2011;Zhou et al 2014;Nakano et al 2016;Vergadi et al 2017;Dean et al 2019).…”

Tricarboxylic acid cycle metabolites in the control of macrophage activation and effector phenotypes

“…Within the innate immune system, macrophages contribute to normal physiologic processes such as organ development, tissue homeostasis, defense against pathogens, and resolution of inflammation . When these same processes are overwhelmed or subverted, however, macrophages promote maladaptive responses leading to pathologies such as heart disease, inflammation, autoimmunity, and cancer …”

“…3,4 When these same processes are overwhelmed or subverted, however, macrophages promote maladaptive responses leading to pathologies such as heart disease, inflammation, autoimmunity, and cancer. [5][6][7] Macrophage phenotypic plasticity enables them to adapt to and acquire very specific effector functions as diverse as pathogen clearance, wound repair, neoangiogenesis, antigen presentation, and immune evasion. 8 Although specific plasticity outcomes and effector functions are traditionally thought to be determined by microenvironmental-specific stimuli such as Th1/Th2 cytokine patterns and/or specific bacterial byproducts, many recent studies implicate accompanying changes in metabolic pathways as being critically important determinants of specific macrophage polarization phenotypes.…”

MiR-202-5p Promotes M2 Polarization in Allergic Rhinitis by Targeting MATN2

“…Not only might intracellular kinases and transcription factors control the activation and polarization of macrophages [8, 9], but also microRNAs (miRNAs) emerge as critical regulators to rewire functional phenotypes of macrophages [10-12], which could be utilized as biomarkers or therapeutic targets against diverse immunologic and inflammatory diseases. While little miRNA research has been done in AR, the aim of this investigation is to determine the role of miR-202-5p in AR.…”