Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Erik Renström

Erik Renström

Vice-chancellor

Erik Renström

MafA expression preserves immune homeostasis in human and mouse islets

Author

  • Tania Singh
  • Luis Sarmiento
  • Cheng Luan
  • Rashmi B. Prasad
  • Jenny Johansson
  • Luis R. Cataldo
  • Erik Renström
  • Shamit Soneji
  • Corrado Cilio
  • Isabella Artner

Summary, in English

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.

Department/s

  • Endocrine Cell Differentiation and Function
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Diabetes - Immunovirology
  • Diabetes - Islet Patophysiology
  • Genomics, Diabetes and Endocrinology
  • Stem Cell Center
  • Division of Molecular Hematology (DMH)
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy

Publishing year

2018-12-01

Language

English

Publication/Series

Genes

Volume

9

Issue

12

Document type

Journal article

Publisher

MDPI AG

Topic

  • Medical Genetics

Keywords

  • Interferon-induced genes
  • Interferons
  • Islet inflammatory microenvironment
  • Islet of Langerhans
  • MafA transcription factor

Status

Published

Research group

  • Endocrine Cell Differentiation and Function
  • Diabetes - Immunovirology
  • Diabetes - Islet Patophysiology
  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 2073-4425