Interleukin-1 mediates innate immune signaling and antiviral defense in islets

Based on in vitro studies, cytokines are believed to contribute to the pathogenesis of type 1 diabetes by directly causing β-cell damage. In this study, the effects of endogenously produced cytokines, following lipopolysaccharide (LPS) administration to mice, on gene expression in islet cells were evaluated by single-cell RNA sequencing (scRNA-seq). In response to LPS, there is an increase in antiviral and antibacterial genes and repression of genes associated with identity in all endocrine cell populations. While islet-resident non-lymphoid hematopoietic cells were not classically activated, antiviral and antibacterial gene expression was increased. Antipathogen gene expression was also increased in the islet endothelium, while genes associated with transcription, cell migration, and adhesion were decreased. IL-1 was identified as the primary mediator of changes in β-cell gene expression, and we show that IL-1 limits picornavirus replication in islets. Overall, these findings support a role for IL-1-stimulated antipathogen gene expression in β-cells as a physiologically relevant immune-endocrine signaling axis that functions to enhance fitness and reduce susceptibility of these essential cells to virus-mediated damage.