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Loss of MafA and MafB expression promotes islet inflammation.

Singh, Tania LU ; Colberg, Jesper K. LU ; Sarmiento, Luis LU ; Chaves, Patricia LU ; Hansen, Lisbeth LU ; Bsharat, Sara LU ; Cataldo, Luis R. LU ; Dudenhöffer-Pfeifer, Monika LU ; Fex, Malin LU and Bryder, David LU , et al. (2019) In Scientific Reports 9(1).
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... (More)
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. (Less)
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Contribution to journal
publication status
published
subject
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Scientific Reports
volume
9
issue
1
article number
9074
publisher
Nature Publishing Group
external identifiers
  • scopus:85067901306
  • pmid:31235823
ISSN
2045-2322
DOI
10.1038/s41598-019-45528-x
language
English
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yes
id
81f6ec46-c55a-4423-a87a-dc9cad0f98d4
date added to LUP
2019-06-27 09:38:45
date last changed
2020-01-13 02:07:52
@article{81f6ec46-c55a-4423-a87a-dc9cad0f98d4,
  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.},
  author       = {Singh, Tania and Colberg, Jesper K. and Sarmiento, Luis and Chaves, Patricia and Hansen, Lisbeth and Bsharat, Sara and Cataldo, Luis R. and Dudenhöffer-Pfeifer, Monika and Fex, Malin and Bryder, David and Holmberg, Dan and Sitnicka, Ewa and Cilio, Corrado and Prasad, Rashmi B. and Artner, Isabella},
  issn         = {2045-2322},
  language     = {eng},
  month        = {06},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Loss of MafA and MafB expression promotes islet inflammation.},
  url          = {http://dx.doi.org/10.1038/s41598-019-45528-x},
  doi          = {10.1038/s41598-019-45528-x},
  volume       = {9},
  year         = {2019},
}