Implications of macrophage polarization in autoimmunity

Abstract

Macrophages 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.

Keywords: M1; M2; autoimmunity; macrophage alternative activation; macrophage polarization.

Figure 1

M1 (pro‐inflammatory)/M2 (anti‐inflammatory) macrophage phenotypes paradigm is reviewed. Both types of macrophages represent opposite ends of a continuum of intermediate phenotypes and are produced after monocyte stimulation with lipopolysaccharide (LPS)/interferon‐γ (IFN‐γ) (M1) or interleukin‐10 (IL‐10)/IL‐4 (M2). Haem‐oxygenase 1 (HO‐1) higher expression in M2 macrophages is schematically represented. Characteristic M1 pro‐inflammatory profile is beneficial for pathogens/tumour elimination but is detrimental for the wound healing process. On the other hand, M2 anti‐inflammatory profile improves chronic inflammatory diseases and regeneration.

Figure 2

Snapshot of polarization observed in tissues may be the result of new monocyte‐derived macrophages arrival and/or polarization of pre‐existing tissue‐resident macrophages towards another profile. Different stimuli as pathogens or wounds are the forces driving this process. The respective increase of pro‐inflammatory M1 (a) or anti‐inflammatory M2 phenotype (b) is represented in the figure as the result of both contributions.