Investigation of Wnt2‘s Role in Macrophage Polarization and Its Effects on Sepsis

Objective Sepsis, characterized by organ dysfunction from an uncontrolled immune response to infection, remains a leading cause of mortality in critical care settings. A key underlying mechanism involves the imbalance between pro-inflammatory M1-type macrophages and anti-inflammatory M2-type macrophages in the biphasic pathological process of ‘cytokine storm–immunosuppression’ in sepsis. These macrophages, as crucial effector cells of innate immunity, contribute to multi-organ injury.Methods This article presents a comprehensive review of a large body of relevant literature. Wnt2, a secreted glycoprotein from the Wnt signaling family, performs distinct immunomodulatory roles. The classic Wnt/β-catenin signaling pathway interacts with key regulatory nodes like NF-κB and metabolic reprogramming to regulate macrophage phenotype switching, balance inflammatory cytokine release, and protect organs including the lungs, intestines, heart, and liver during sepsis.Results This article provides a comprehensive overview of the molecular characteristics of Wnt2, the pathological significance of macrophage polarization in sepsis, the molecular network underlying Wnt2-mediated macrophage polarization and inflammatory regulation, and the prospects for clinical translation.Conclusions The study establishes an integrative framework linking ‘Wnt/β-catenin–macrophage polarization–sepsis,’ providing a theoretical basis for the development of targeted immunotherapeutic strategies for sepsis.