MafA Expression Preserves Immune Homeostasis in Human and Mouse Islets.

Type 1 (T1D) and type 2 (T2D) diabetes are triggered by a combination of environmental and/or genetic factors. Maf transcription factors regulate pancreatic beta (β)-cell function, and have also been implicated in the regulation of immunomodulatory cytokines like interferon-β (IFNβ1). In this study, we assessed and co-expression with pro-inflammatory cytokine signaling genes in RNA-seq data from human pancreatic islets. Interestingly, expression was strongly negatively correlated with cytokine-induced signaling (such as , ) and T1D susceptibility genes (), whereas correlation of these genes with was weaker. In order to evaluate if the loss of MafA altered the immune status of islets, deficient mouse islets () were assessed for inherent anti-viral response and susceptibility to enterovirus infection. deficient mouse islets had elevated basal levels of , ( in humans), and () which resulted in reduced virus propagation in response to coxsackievirus B3 (CVB3) infection. Moreover, an acute knockdown of MafA in β-cell lines also enhanced Rig1 and Mda5 protein levels. Our results suggest that precise regulation of MAFA levels is critical for islet cell-specific cytokine production, which is a critical parameter for the inflammatory status of pancreatic islets.