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Loss of MafA and MafB expression promotes islet inflammation.

Published on Dec 1, 2019in Scientific Reports4.011
· DOI :10.1038/s41598-019-45528-x
Tania Singh3
Estimated H-index: 3
,
Jesper K. Colberg1
Estimated H-index: 1
(Lund University)
+ 12 AuthorsIsabella Artner15
Estimated H-index: 15
Abstract
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 naive 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.
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#1W. Nicholas Haining (MIT: Massachusetts Institute of Technology)H-Index: 34
#2Sarah A. Weiss (Harvard University)H-Index: 3
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