IL-27 is a member of the IL-12 family, consisting of Ebi3 and IL-27p28. It binds to IL-27rα and gp130, activating downstream signaling pathways such as MAPK, NF-κB, and STATs, which regulate innate and adaptive immune responses. IL-27 has dual roles in inflammatory autoimmune diseases, acting both pro-inflammatory and anti-inflammatory. In monocytes, IL-27 promotes pro-inflammatory activity by increasing IFNγ, TNFα, and IL-6 expression, while also suppressing apoptosis. In macrophages, IL-27 can both inhibit and promote function, influencing foam cell formation and autophagy. In dendritic cells, IL-27 regulates cytokine production and antigen presentation, with some studies showing inhibitory effects and others showing promoting effects. In neutrophils, IL-27 has anti-inflammatory roles, reducing ROS and POX production. In natural killer (NK) cells, IL-27 enhances effector function, increasing cytotoxicity and IFNγ production. IL-27 also regulates eosinophil and mast cell functions, with effects on eosinophil activation and mast cell inhibition. In adaptive immunity, IL-27 promotes Th1 cell differentiation and function, while inhibiting Th2 and Th17 cell differentiation. In mouse models, IL-27 promotes Th1 and Th2 cell differentiation, while inhibiting Th17, Th9, and Tfh cell differentiation. Overall, IL-27 plays a complex role in immune regulation, with potential therapeutic applications in inflammatory autoimmune disorders.IL-27 is a member of the IL-12 family, consisting of Ebi3 and IL-27p28. It binds to IL-27rα and gp130, activating downstream signaling pathways such as MAPK, NF-κB, and STATs, which regulate innate and adaptive immune responses. IL-27 has dual roles in inflammatory autoimmune diseases, acting both pro-inflammatory and anti-inflammatory. In monocytes, IL-27 promotes pro-inflammatory activity by increasing IFNγ, TNFα, and IL-6 expression, while also suppressing apoptosis. In macrophages, IL-27 can both inhibit and promote function, influencing foam cell formation and autophagy. In dendritic cells, IL-27 regulates cytokine production and antigen presentation, with some studies showing inhibitory effects and others showing promoting effects. In neutrophils, IL-27 has anti-inflammatory roles, reducing ROS and POX production. In natural killer (NK) cells, IL-27 enhances effector function, increasing cytotoxicity and IFNγ production. IL-27 also regulates eosinophil and mast cell functions, with effects on eosinophil activation and mast cell inhibition. In adaptive immunity, IL-27 promotes Th1 cell differentiation and function, while inhibiting Th2 and Th17 cell differentiation. In mouse models, IL-27 promotes Th1 and Th2 cell differentiation, while inhibiting Th17, Th9, and Tfh cell differentiation. Overall, IL-27 plays a complex role in immune regulation, with potential therapeutic applications in inflammatory autoimmune disorders.