
Luis Sarmiento-Pérez
Assistant researcher

Loss of MafA and MafB expression promotes islet inflammation.
Author
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