Format

Send to

Choose Destination
Nat Immunol. 2009 Sep;10(9):1026-33. doi: 10.1038/ni.1773. Epub 2009 Aug 9.

Deaf1 isoforms control the expression of genes encoding peripheral tissue antigens in the pancreatic lymph nodes during type 1 diabetes.

Author information

1
Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA.

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.

PMID:
19668219
PMCID:
PMC2752139
DOI:
10.1038/ni.1773
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center