nih-gov/researchfestival.nih.gov/2015/posters/deletion-ifn-gamma-3-utr-au-rich-element-results-autoimmune-cholangitis
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<title>Deletion of the IFN-gamma 3 UTR AU-rich element results in autoimmune cholangitis in female C57/BL6 mice | NIH Research Festival</title>
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<article><div class="banner banner--gray banner--compact" style="--banner-background-image: url('/sites/default/files/media/image/2021-03/2015.jpg');--banner-background-focus: 50% 50%"><div class="banner__wrapper"><div class="banner__container"><h2 class="banner__heading">NIH Research Festival</h2><div class="banner__content"><p><strong><time datetime="2015-09-16">September 16</time> <time datetime="2015-09-18">18, 2015</time></strong></p></div></div></div></div></article>
<div class="section"><div data-drupal-messages-fallback class="hidden"></div></div><main role="main"><div id="main-content" tabindex="-1"></div><div class="section"><div class="content-sidebar"><div class="content-sidebar__main"><div class="content-sidebar__main-content"><div id="block-mainpagecontent-2"><article><h1>Deletion of the IFN-gamma 3 UTR AU-rich element results in autoimmune cholangitis in female C57/BL6 mice</h1><div class="schedule"><div class="schedule__label"><div class="schedule__label-text"><time datetime="2015-09-17">Thursday, September 17, 2015</time>
Poster Session III
</div></div><div class="schedule__content"><div class="schedule__item"><div class="schedule__time">3:30 5:00 p.m.</div><div class="schedule__description"><p><strong>FAES Terrace</strong></p></div><div class="schedule__description"><p><strong>NCI</strong></p></div><div class="schedule__description"><p><strong>IMMUNO-1</strong></p></div></div></div></div><p><strong>FARE Award Winner</strong></p><h2>Authors</h2><ul><li>H Bae</li><li>JC Valencia</li><li>DL Hodge</li><li>T Back</li><li>M Karwan</li><li>D Feng</li><li>B Gao</li><li>O Park</li><li>K Tsuneyama</li><li>PS Leung</li><li>ME Gershwin</li><li>HA Young</li></ul><h2>Abstract</h2><p>Primary biliary cirrhosis (PBC) is an autoimmune liver disease and occurs primarily in women (&gt; 90%). PBC is characterized by lymphocytic infiltrates near portal tracts, destruction of small bile ducts and presence of anti-mitochondrial Abs (AMAs), and eventually leads to liver failure. IFN gamma is elevated in patients with PBC, but the functional role of IFN gamma on PBC is not known. Here, we characterized the distinctive pathological phenotype of PBC in a mouse model of chronic IFN gamma expression generated by deletion of the IFN-gamma 3 UTR AU-rich element. Histological assessment of the liver shows that female ARE-Del mice have moderate immune cell infiltration and bile duct destruction near portal tracts. Consistent with clinical features seen in PBC, female ARE-Del have over 30 fold upregulated total bile acids and spontaneous production of AMAs in serum. In contrast, male ARE-Del have mild histological and serological evidence of PBC. To investigate the mechanisms involved in PBC development, we analyzed liver gene expression in ARE-Del mice using RNA-sequencing. By focusing on genes whose expression is highly specific to female ARE-Del, we determined that IFN gamma and interferon alpha receptor are top upstream regulators for this female specific disease progression based on pathway analysis. Remarkably, deletion of the interferon alpha receptor in ARE-Del mice significantly reversed the pathological phenotypes of PBC. Taken together, the ARE-Del mice model mimics the features presented in human PBC and demonstrates that the IFN signature is critical in PBC progression.</p><p><strong>Scientific Focus Area</strong>: Immunology</p><p class="updated"><small>This page was last updated on Friday, March 26, 2021</small></p></article>
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