Modulation of macrophage polarization towards anti-inflammatory M2 phenotype (M2 polarization)

Macrophage polarization is the process by which macrophages transition between functional states, primarily the pro-inflammatory M1 and the anti-inflammatory M2 phenotypes, in response to environmental cues (Murray, 2017, Annual Review of Physiology). The M2 phenotype, often induced by cytokines like IL-4 and IL-13, is essential for the resolution of inflammation, tissue repair, and maintaining immune homeostasis (Sica & Mantovani, 2012, Journal of Clinical Investigation). Therapeutic modulation aimed at shifting macrophages toward the M2 state is a promising strategy for treating chronic inflammatory conditions such as rheumatoid arthritis and atherosclerosis (Odegaard et al., 2007, Nature). However, this approach must be carefully managed, as M2-like tumor-associated macrophages (TAMs) are known to facilitate tumor progression, angiogenesis, and immune evasion in the cancer microenvironment (Mantovani et al., 2002, Nature Reviews Immunology). Key molecular drivers involved in this polarization include the IL-4 receptor/STAT6 axis, PPAR-gamma, and various metabolic and epigenetic regulators (Martinez & Gordon, 2014, F1000Prime Reports).

Other names

Alternative macrophage activationM1-to-M2 macrophage transitionPro-resolving macrophage polarizationM2a/b/c/d polarization

Activation of specific transcription factors such as Signal transducer and activator of transcription 6 (STAT6), Peroxisome proliferator-activated receptor gamma (PPAR-gamma), and Interferon regulatory factor 4 (IRF4) to induce an anti-inflammatory gene expression profile.