IL15 is a pleiotropic cytokine that drives inflammatory and protective immune responses through trans-presentation via its high-affinity receptor IL15RA on cell surfaces, rather than soluble secretion like most cytokines 12. IL15 stimulates proliferation of natural killer cells, T cells, and B cells while promoting cytokine secretion including IL-8 and CCL2 from monocytes to recruit immune cells to infection sites 34. Signaling occurs through JAK-STAT phosphorylation cascades, particularly JAK1/JAK3 activation leading to STAT3/STAT5 recruitment 5. Mechanistically, IL15 regulates immune cell differentiation and survival; uterine NK cell differentiation during endometrial regeneration is IL15-driven 6, and IL15 protects cryopreserved NK cells from granzyme B-mediated apoptosis 7. Clinically, IL15 is central to coeliac disease pathogenesis, with overexpression in gut epithelium and lamina propria driving villous atrophy through CD4+ T cell and HLA-DQ8-dependent mechanisms 8. Therapeutically, IL15 enhances CAR-T cell expansion and antitumor activity; IL15-engineered GPC3 CAR-T cells achieved 33% antitumor response rates in solid cancers 9, and IL15/IL21-coexpressing GPC3-CAR T cells demonstrated superior persistence against hepatocellular carcinoma 10. IL15 also potentiates NK cell-based immunotherapy and enhances antibody-dependent cellular cytotoxicity 1112. Sex hormone modulation affects IL15 production, with testosterone increasing monocyte-derived IL15 13.