Comparative Transcriptomic Profiling Identifies IL-1β as a Non-Canonical Driver of Human Dendritic Cell Maturation.

Background: Dendritic cell (DC) maturation is traditionally triggered by pathogen-associated molecular patterns (PAMPs) through Toll-like receptors. However, emerging evidence suggests that the cytokine interleukin-1β (IL-1β) can act independently of PAMPs to drive DC activation and T cell priming. Objectives: This study aimed to perform a comparative transcriptomic analysis of IL-1β- and R848-induced maturation in human DCs to uncover shared and distinct molecular signatures underlying these activation pathways. Materials and Methods: RNA-seq data from dataset GSE108526 were analyzed following normalization and quality control. Differential gene expression was assessed using a linear model incorporating both treatment type and timepoint as factors. Functional enrichment analyses were conducted to identify pathways and biological processes enriched under each condition. Results: Both IL-1β and R848 activated core immune response programs, yet exhibited distinct transcriptional emphases. IL-1β preferentially upregulated genes associated with cytokine regulation, surface receptor signaling, and cell communication, whereas R848 induced stronger interferon-stimulated gene networks and antiviral defense pathways. Comparative visualization of key maturation, cytokine, and IL-2 receptor genes revealed overlapping but stimulus-specific expression profiles. Conclusions: The findings highlight that IL-1β can substitute for PAMPs in inducing DC activation, yet orchestrates a unique immune transcriptional landscape. This suggests a specialized immunomodulatory potential for IL-1β distinct from classical TLR-mediated pathways.