Biology and clinical relevance of granulysin

Granulysin is a cytolytic and proinflammatory molecule first identified by a screen for genes expressed ‘late’ (3–5 days) after activation of human peripheral blood mononuclear cells. Granulysin is present in cytolytic granules of cytotoxic T lymphocytes and natural killer cells. Granulysin is made in a 15‐kDa form that is cleaved into a 9‐kDa form at both the amino and the carboxy termini. The 15‐kDa form is constitutively secreted, and its function remains poorly understood. The 9‐kDa form is released by receptor‐mediated granule exocytosis. Nine kiloDalton granulysin is broadly cytolytic against tumors and microbes, including gram‐positive and gram‐negative bacteria, fungi/yeast and parasites. It kills the causative agents of both tuberculosis and malaria. Granulysin is also a chemoattractant for T lymphocytes, monocytes and other inflammatory cells and activates the expression of a number of cytokines, including regulated upon activation T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)‐1, MCP‐3, macrophage inflammatory protein (MIP)‐1α, interleukin (IL)‐10, IL‐1, IL‐6 and interferon (IFN)‐α. Granulysin is implicated in a myriad of diseases including infection, cancer, transplantation, autoimmunity, skin and reproductive maladies. Small synthetic forms of granulysin are being developed as novel antibiotics. Studies of the full‐length forms may give rise to new diagnostics and therapeutics for use in a wide variety of diseases.