M2 microglial polarization

M2 microglial polarization refers to the alternative activation state of microglia, the resident immune cells of the central nervous system. Unlike the pro-inflammatory M1 state, M2 polarization is associated with anti-inflammatory signaling, tissue repair, and neuroprotection [PubMed: 25114441]. This phenotypic switch is typically induced by cytokines such as interleukin-4 (IL-4) and interleukin-10 (IL-10), which trigger downstream signaling pathways like JAK/STAT6 [PubMed: 30416345]. In the context of neurodegenerative diseases and stroke, promoting M2 polarization is a major therapeutic strategy aimed at resolving chronic inflammation and enhancing neuronal survival. Drugs like PPAR-gamma agonists and certain sphingosine-1-phosphate receptor modulators have shown the ability to shift microglia toward this beneficial phenotype [PubMed: 31057378]. However, the M1/M2 dichotomy is increasingly viewed as a simplification of a more complex spectrum of activation states in vivo. Monitoring this polarization often involves measuring biomarkers such as CD206, Arginase-1, and Ym1 [PubMed: 28507567].

Other names

Alternative activation of microgliaAnti-inflammatory microglial phenotypeM2-like microglial stateNeuroprotective microglial phenotype

Promotion of M2 polarization is typically achieved by activating the IL-4R/STAT6 signaling pathway, stimulating PPAR-gamma receptors, or modulating sphingosine-1-phosphate receptors to inhibit pro-inflammatory NF-kappaB signaling and enhance expression of anti-inflammatory genes [PubMed: 30416345, 31057378].