We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Deaf1 isoforms control the expression of genes encoding peripheral tissue antigens in the pancreatic lymph nodes during type 1 diabetes.
- Authors
Yip, Linda; Su, Leon; Sheng, Deqiao; Chang, Pearl; Atkinson, Mark; Czesak, Margaret; Albert, Paul R; Collier, Ai-Ris; Turley, Shannon J; Fathman, C Garrison; Creusot, Rémi J
- Abstract
Type 1 diabetes may result from a breakdown in peripheral tolerance that is partially controlled by the expression of peripheral tissue antigens (PTAs) in lymph nodes. Here we show that the transcriptional regulator Deaf1 controls the expression of genes encoding PTAs in the pancreatic lymph nodes (PLNs). The expression of canonical Deaf1 was lower, whereas that of an alternatively spliced variant was higher, during the onset of destructive insulitis in the PLNs of nonobese diabetic (NOD) mice. We identified an equivalent variant Deaf1 isoform in the PLNs of patients with type 1 diabetes. Both the NOD mouse and human Deaf1 variant isoforms suppressed PTA expression by inhibiting the transcriptional activity of canonical Deaf1. Lower PTA expression resulting from the alternative splicing of DEAF1 may contribute to the pathogenesis of type 1 diabetes.
- Publication
Nature immunology, 2009, Vol 10, Issue 9, p1026
- ISSN
1529-2916
- Publication type
Journal Article
- DOI
10.1038/ni.1773