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Nature Research, Nature Immunology, 9(10), p. 1026-1033, 2009

DOI: 10.1038/ni.1773

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

Journal article published in 2009 by Linda Yip, Leon Su ORCID, Deqiao Sheng, Pearl Chang, Mark Atkinson, Margaret Czesak, Paul R. Albert, Ai-Ris Collier, Shannon J. Turley, C. Garrison Fathman, Rémi J. Creusot ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.