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Luis Sarmiento-Pérez

Assistant researcher

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Loss of MafA and MafB expression promotes islet inflammation.

Author

  • Tania Singh
  • Jesper K. Colberg
  • Luis Sarmiento
  • Patricia Chaves
  • Lisbeth Hansen
  • Sara Bsharat
  • Luis R. Cataldo
  • Monika Dudenhöffer-Pfeifer
  • Malin Fex
  • David Bryder
  • Dan Holmberg
  • Ewa Sitnicka
  • Corrado Cilio
  • Rashmi B. Prasad
  • Isabella Artner

Summary, in English

Maf transcription factors are critical regulators of beta-cell function. We have previously shown that reduced MafA expression in human and mouse islets is associated with a pro-inflammatory gene signature. Here, we investigate if the loss of Maf transcription factors induced autoimmune processes in the pancreas. Transcriptomics analysis showed expression of pro-inflammatory as well as immune cell marker genes. However, clusters of CD4+ T and B220+ B cells were associated primarily with adult MafA-/-MafB+/-, but not MafA-/- islets. MafA expression was detected in the thymus, lymph nodes and bone marrow suggesting a novel role of MafA in regulating immune-cell function. Analysis of pancreatic lymph node cells showed activation of CD4+ T cells, but lack of CD8+ T cell activation which also coincided with an enrichment of naïve CD8+ T cells. Further analysis of T cell marker genes revealed a reduction of T cell receptor signaling gene expression in CD8, but not in CD4+ T cells, which was accompanied with a defect in early T cell receptor signaling in mutant CD8+ T cells. These results suggest that loss of MafA impairs both beta- and T cell function affecting the balance of peripheral immune responses against islet autoantigens, resulting in local inflammation in pancreatic islets.

Department/s

  • Stem Cell Center
  • Endocrine Cell Differentiation and Function
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
  • Diabetes - Immunovirology
  • Autoimmunity
  • Diabetes - Molecular Metabolism
  • Developmental Hematopoiesis
  • Lymphoid Development and Regulation
  • Genomics, Diabetes and Endocrinology

Publishing year

2019-06-24

Language

English

Publication/Series

Scientific Reports

Volume

9

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Endocrine Cell Differentiation and Function
  • Diabetes - Immunovirology
  • Autoimmunity
  • Diabetes - Molecular Metabolism
  • Developmental Hematopoiesis
  • Lymphoid Development and Regulation
  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 2045-2322