Alternatively activated microglia (M2 phenotype) (M2 microglia)

The M2 phenotype of microglia, often termed the alternatively activated state, represents a neuroprotective and anti-inflammatory activation profile of the resident macrophages in the central nervous system. Unlike the classically activated M1 state, M2 microglia are primarily involved in the resolution of inflammation, clearance of cellular debris (such as amyloid-beta or myelin fragments), and the secretion of trophic factors that support neuronal survival and tissue repair (Tang and Le, 2016). This phenotype is characterized by the expression of specific markers, including the mannose receptor CD206, Arginase-1, and anti-inflammatory cytokines like IL-10 and TGF-beta (Cherry et al., 2014). In many neurodegenerative and neuroinflammatory diseases, the microglial population shifts toward a chronic M1 state, which contributes to progressive neuronal damage. Consequently, the M2 phenotype is a major therapeutic target for pharmacological intervention, with agents like IL-4, PPAR-gamma agonists, and immunomodulators like Glatiramer acetate used to shift polarization in favor of repair (Orihuela et al., 2016). However, modern single-cell transcriptomics suggest that the M1/M2 dichotomy is an oversimplification, as microglia in the human brain often exist in a complex spectrum of activation states. While targeting the M2 state remains a promising approach for treating stroke and Alzheimer's disease, researchers must address the challenge of phenotypic stability and the potential for these cells to promote tumor progression in the context of brain cancer.

Other names

M2-like microgliaAnti-inflammatory microgliaPro-repair microgliaAlternatively activated stateM2-polarized microglia

Therapeutic strategies focus on promoting the polarization of microglia from a pro-inflammatory M1-like state to an anti-inflammatory, neuroprotective M2-like state. This is often achieved through the activation of STAT6 signaling by IL-4 or the activation of PPAR-gamma, which suppresses pro-inflammatory gene transcription and enhances the expression of genes involved in tissue remodeling and phagocytosis (Cherry et al., 2014; Orihuela et al., 2016).