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Genes 2018, 9(12), 644; https://doi.org/10.3390/genes9120644

MafA Expression Preserves Immune Homeostasis in Human and Mouse Islets

1
Stem Cell Center, Lund University, 22184 Lund, Sweden
2
Lund University Diabetes Centre, 22184 Lund, Sweden
*
Author to whom correspondence should be addressed.
Received: 29 November 2018 / Accepted: 12 December 2018 / Published: 18 December 2018
(This article belongs to the Section Human Genomics and Genetic Diseases)
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Abstract

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 MAFA and MAFB co-expression with pro-inflammatory cytokine signaling genes in RNA-seq data from human pancreatic islets. Interestingly, MAFA expression was strongly negatively correlated with cytokine-induced signaling (such as IFNAR1, DDX58) and T1D susceptibility genes (IFIH1), whereas correlation of these genes with MAFB was weaker. In order to evaluate if the loss of MafA altered the immune status of islets, MafA deficient mouse islets (MafA−/−) were assessed for inherent anti-viral response and susceptibility to enterovirus infection. MafA deficient mouse islets had elevated basal levels of Ifnβ1, Rig1 (DDX58 in humans), and Mda5 (IFIH1) 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. View Full-Text
Keywords: islet of Langerhans; MafA transcription factor; islet inflammatory microenvironment; interferons; interferon-induced genes islet of Langerhans; MafA transcription factor; islet inflammatory microenvironment; interferons; interferon-induced genes
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Singh, T.; Sarmiento, L.; Luan, C.; Prasad, R.B.; Johansson, J.; Cataldo, L.R.; Renström, E.; Soneji, S.; Cilio, C.; Artner, I. MafA Expression Preserves Immune Homeostasis in Human and Mouse Islets. Genes 2018, 9, 644.

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