IL4 is a pleiotropic cytokine secreted by mast cells, T cells, eosinophils, and basophils that orchestrates immune responses through JAK-STAT signaling 1. Upon binding to IL4R, IL4 forms either a type 1 receptor complex with IL2RG (predominantly on hematopoietic cells) or a type 2 complex with IL13RA1 (on both hematopoietic and non-hematopoietic cells), both activating JAK3/JAK1 and STAT6 phosphorylation 23. IL4 drives Th2 differentiation, IgE and IgG1 class switching in B cells, and M2 macrophage polarization 4. It enhances CD23 expression on lymphocytes and monocytes, induces dendritic cell autophagy via mTORC1 interference, and plays critical roles in cognition and memory 5. Therapeutically, IL4 shows promise in sepsis management through trained immunity induction in myeloid cells 6 and cardiometabolic disease control via exosome-mediated macrophage reprogramming 7. IL4-educated macrophages demonstrate anti-inflammatory, epithelial reparative, and anticolitic functions relevant to inflammatory bowel disease treatment 8. Conversely, IL4 promotes hepatocellular carcinoma sorafenib resistance by driving macrophage extracellular trap formation via the PADI4 pathway 9. These dual roles highlight IL4's context-dependent immunomodulatory functions in health and disease.