Interleukin-27 (IL-27) is a heterodimeric cytokine consisting of Epstein–Barr virus (EBV)-induced gene 3 (Ebi3) and IL-27p28. IL-27 binds to receptors IL-27α and gp130, regulating downstream signaling pathways such as MAPK, NF-κB, and STATs. IL-27 is abnormal in various inflammatory autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. It plays both pro-inflammatory and anti-inflammatory roles by regulating innate and adaptive immune responses. In monocytes, IL-27 promotes pro-inflammatory activity, while in macrophages, it has a dual role, inhibiting and promoting functions. In dendritic cells (DCs), IL-27 regulates antigen processing and T-cell stimulation. In neutrophils, IL-27 plays an anti-inflammatory role, reducing neutrophil numbers and activity. In natural killer (NK) cells, IL-27 enhances effector functions. In eosinophils, IL-27 regulates their function, and in mast cells, it inhibits allergic responses. In adaptive immunity, IL-27 promotes Th1 cell differentiation and function, while inhibiting Th2 and Th17 cell functions. These findings highlight the complex and multifaceted role of IL-27 in inflammatory autoimmune diseases, suggesting potential therapeutic targets for future treatments.Interleukin-27 (IL-27) is a heterodimeric cytokine consisting of Epstein–Barr virus (EBV)-induced gene 3 (Ebi3) and IL-27p28. IL-27 binds to receptors IL-27α and gp130, regulating downstream signaling pathways such as MAPK, NF-κB, and STATs. IL-27 is abnormal in various inflammatory autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. It plays both pro-inflammatory and anti-inflammatory roles by regulating innate and adaptive immune responses. In monocytes, IL-27 promotes pro-inflammatory activity, while in macrophages, it has a dual role, inhibiting and promoting functions. In dendritic cells (DCs), IL-27 regulates antigen processing and T-cell stimulation. In neutrophils, IL-27 plays an anti-inflammatory role, reducing neutrophil numbers and activity. In natural killer (NK) cells, IL-27 enhances effector functions. In eosinophils, IL-27 regulates their function, and in mast cells, it inhibits allergic responses. In adaptive immunity, IL-27 promotes Th1 cell differentiation and function, while inhibiting Th2 and Th17 cell functions. These findings highlight the complex and multifaceted role of IL-27 in inflammatory autoimmune diseases, suggesting potential therapeutic targets for future treatments.