Loss of MafA and MafB expression promotes islet inflammation.
Sci Rep
; 9(1): 9074, 2019 06 24.
Article
em En
| MEDLINE
| ID: mdl-31235823
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 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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
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Ilhotas Pancreáticas
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Fatores de Transcrição Maf Maior
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Fator de Transcrição MafB
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article