Emerging Insights into the Interplay Between PANoptosis and Autophagy in Immune Regulation and Immune-Mediated Inflammatory Diseases

PANoptosis is an integrated form of regulated cell death that combines pyroptosis, apoptosis, and necroptosis through a coordinated molecular platform known as the PANoptosome. Autophagy, in parallel, maintains immune homeostasis by controlling cellular stress responses. Although both pathways are essential for innate and adaptive immunity, their functional interplay has only recently been explored. This review summarizes current knowledge on the bidirectional relationship between PANoptosis and autophagy, with emphasis on how autophagy can restrain PANoptotic signaling or, under certain conditions, promote inflammatory cell death. We discuss cell-type-specific aspects of this crosstalk in macrophages, dendritic cells, monocytes, neutrophils, T cells, and B cells, focusing on key PANoptosis mediators and autophagy-related proteins. We then examine how dysregulated autophagy and exaggerated PANoptotic signaling contribute to chronic inflammation and tissue damage in immune-mediated inflammatory disease, including systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, psoriasis, and inflammatory bowel disease. Finally, we outline shared molecular principles that position the autophagy-PANoptosis axis as a fundamental immunoregulatory mechanism and a promising source of therapeutic targets in chronic inflammatory and autoimmune disorders.