Deaf1 isoforms control the expression of genes encoding peripheral tissue antigens in the pancreatic lymph nodes during type 1 diabetes.
Deaf1 isoforms control the expression of genes encoding peripheral tissue antigens in the pancreatic lymph nodes during type 1 diabetes.
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1型糖尿病（T1D）可能是由外周耐受性的破坏引起的，外周耐受性部分受淋巴结中外周组织抗原（PTA）表达的控制。在这里，我们表明，转录调节因子变形表皮自动调节因子1（Deaf 1）控制PTA基因在胰腺淋巴结（PLN）的表达。典型的Deaf 1的表达减少，而选择性剪接的变体增加破坏性胰岛炎在PLN的NOD小鼠发病期间。在T1D患者的PLN中鉴定了等效变体Deaf 1同种型。NOD和人类Deaf 1变体亚型通过抑制经典Deaf 1的转录活性来抑制PTA表达。由Deaf1的选择性剪接导致的PTA表达减少可能有助于T1D发病机制。
Type 1 diabetes (T1D) may result from a breakdown in peripheral tolerance that is partially controlled by peripheral tissue antigen (PTA) expression in lymph nodes. Here we show that the transcriptional regulator deformed epidermal autoregulatory factor 1 (Deaf1) controls PTA gene expression in the pancreatic lymph nodes (PLN). The expression of canonical Deaf1 was reduced, while that of an alternatively spliced variant was increased during the onset of destructive insulitis in the PLN of NOD mice. An equivalent variant Deaf1 isoform was identified in the PLN of T1D patients. Both NOD and human Deaf1 variant isoforms suppressed PTA expression by inhibiting the transcriptional activity of canonical Deaf1. Reduced PTA expression resulting from the alternative splicing of Deaf1 may contribute to T1D pathogenesis.
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DOI：
10.1126/science.1159407
发表时间：
2008-08-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gardner JM;Devoss JJ;Friedman RS;Wong DJ;Tan YX;Zhou X;Johannes KP;Su MA;Chang HY;Krummel MF;Anderson MS
通讯作者：
Anderson MS
影响因子：
3.5
作者：
BORSI, L;CASTELLANI, P;ZARDI, L
通讯作者：
ZARDI, L
DOI：
10.1084/jem.20030413
发表时间：
2003-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Avichezer D;Grajewski RS;Chan CC;Mattapallil MJ;Silver PB;Raber JA;Liou GI;Wiggert B;Lewis GM;Donoso LA;Caspi RR
通讯作者：
Caspi RR
影响因子：
7.7
作者：
Org, Tonis;Chignola, Francesca;Peterson, Paert
通讯作者：
Peterson, Paert
影响因子：
5.3
作者：
Hahm, KM;Sum, EYM;Orkin, SH
通讯作者：
Orkin, SH