Inflammatory cytokine pathways via macrophage polarization

Inflammatory cytokine pathways via macrophage polarization refer to the complex signaling networks that govern the functional plasticity of macrophages (Murray, P. J., 2017, Nature Reviews Immunology). Macrophages can polarize into two main phenotypes: the classically activated M1 state, which produces pro-inflammatory cytokines (e.g., TNF, IL-12) to combat pathogens, and the alternatively activated M2 state, which produces anti-inflammatory cytokines (e.g., IL-10, TGF-beta) to promote tissue repair (Sica, A., & Mantovani, A., 2012, Journal of Clinical Investigation). This polarization is regulated by various stimuli, including cytokines, toll-like receptor (TLR) ligands, and metabolic signals, which activate specific transcription factors like NF-kappaB, STAT1, and STAT6 (Yunna, C., et al., 2020, Biomolecules). In many diseases, such as cancer and chronic inflammatory disorders, the balance between M1 and M2 polarization is disrupted, leading to persistent inflammation or immune evasion (Biswas, S. K., & Mantovani, A., 2010, Nature Immunology). Consequently, targeting these pathways to 're-polarize' macrophages has become a significant area of therapeutic interest, utilizing drugs like JAK inhibitors or CSF1R antagonists to modulate the immune microenvironment (Cassetta, L., & Pollard, J. W., 2018, Nature Reviews Drug Discovery). Therapeutic modulation aims to either enhance the M1 phenotype for anti-tumor activity or promote the M2 phenotype to resolve chronic inflammation and fibrosis (Mantovani, A., et al., 2017, Nature Reviews Rheumatology). Understanding the crosstalk between these pathways is essential for developing precision immunotherapies that can selectively alter macrophage function without causing broad immunosuppression (Ruytinx, P., et al., 2018, Frontiers in Immunology).

Other names

Macrophage polarizationM1/M2 macrophage activationMacrophage functional plasticityMacrophage polarization signaling

Modulation of intracellular signaling cascades (e.g., JAK/STAT, NF-kappaB, MAPK) and nuclear receptors (e.g., PPAR-gamma) to shift the functional state of macrophages between pro-inflammatory (M1) and anti-inflammatory/pro-resolving (M2) phenotypes.