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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>
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<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>Spontaneous ocular autoimmunity in the absence of Th1 and Th17 effector cytokines</h1><div class="schedule"><div class="schedule__label"><div class="schedule__label-text"><time datetime="2015-09-17">Thursday, September 17, 2015</time>
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– Poster Session III
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</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>NEI</strong></p></div><div class="schedule__description"><p><strong>IMMUNO-3</strong></p></div></div></div></div><h2>Authors</h2><ul><li>SJ Bing</li><li>R Horai</li><li>WP Chong</li><li>P Silver</li><li>Y Jittayasothorn</li><li>CC Chan</li><li>R Caspi</li></ul><h2>Abstract</h2><p>Autoimmune uveitis is a complex group of sight-threatening diseases that arise without known infectious triggers and appear to be T cell-dependent. Studies in uveitis patients and experiments in animal models support the notion that both Th1 and Th17 cells are pathogenic effectors, although some cytokines produced by these subsets can also be protective. Using a recently developed model of spontaneous uveitis in R161H mice that express a transgenic T cell receptor specific for a retinal protein IRBP, we demonstrated that both Th1 and Th17 effectors infiltrate the eyes. To understand how these pathogenic effectors and their respective signature cytokines, IFN-γ or IL-17A, contribute to pathogenesis, we introgressed the retina-specific R161H TCR onto IL-17A-/- and/or IFN-γ-/- (GKO) background. R161H-IL-17A-/- mice developed spontaneous uveitis, similarly to R161H mice, and Th17-polarized R161H-IL-17A-/- T cells transferred disease of similar severity to that of IL-17A-sufficient cells. By contrast, R161H-GKO mice developed significantly attenuated disease with delayed onset, and their T cells polarized under Th1 conditions transferred less severe disease than IFN-γ sufficient R161H T cells. These results suggest that IFN-γ but not IL-17 is a critical pathogenic cytokine in this model, and that Th17-associated effector cytokines other than IL-17A can drive the spontaneous disease. Surprisingly, preliminary data in IL-17A and IFN-γ double deficient R161H (R161H-DKO) show development of moderate to severe disease in the concurrent absence of IFN-γ and IL-17A, despite slightly delayed onset. Further mechanistic studies are ongoing and may uncover novel effector pathway(s) in pathogenesis of autoimmunity.</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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