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- W4313386487 abstract "Abstract Peripheral tolerance is partially controlled by ectopic peripheral tissue antigen (PTA) expression in lymph node stromal cells (LNSCs). We previously showed that the transcriptional regulator deformed epidermal autoregulatory factor 1 (Deaf1) can directly control the transcription and indirectly regulate the processing and/or presentation of PTA genes in LNSCs of the pancreatic lymph nodes (PLN). We showed that Deaf1 is alternatively spliced in the PLN of Non-Obese Diabetic (NOD) mice and Type 1 diabetes (T1D) patients, to form a dominant negative isoform, Deaf1-Var. We previously demonstrated that Deaf1-Var expression was highest in the PLN of NOD mice during the onset of disease, compared to the non-inflamed PLN of healthy age-matched NOD.B10 and NOD.SCID mice. In NOD mice, Deaf1-Var expression in the PLN was found to increase as disease progressed from peri-insulitis to destructive insulitis. In this study, we asked if inflammation induces Deaf1 splicing in the PLN. Deaf1 splicing could be induced in the PLN of NOD.B10 control mice and NOD.SCID mice by i.p. injection of activated splenocytes that home to the PLN. The supernatant of activated splenocytes could also to induce Deaf1 splicing in pancreatic islets, a tissue previously shown to splice >500 genes in response to inflammation. Together, these data suggest that the inflammation that occurs in the PLN during the progression of T1D leads to Deaf1 splicing, loss of Deaf1 function, and reduced PTA expression." @default.
- W4313386487 created "2023-01-06" @default.
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- W4313386487 date "2013-05-01" @default.
- W4313386487 modified "2023-09-27" @default.
- W4313386487 title "Inflammation-induced splicing of Deaf1 in the pancreatic lymph nodes during the progression of Type 1 diabetes (P5061)" @default.
- W4313386487 doi "https://doi.org/10.4049/jimmunol.190.supp.111.13" @default.
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