Interferon-γ regulates discordant mechanisms of uveitis versus joint and axial disease in a murine model resembling spondylarthritis.
Interferon-γ regulates discordant mechanisms of uveitis versus joint and axial disease in a murine model resembling spondylarthritis.
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DOI：
10.1002/art.33404
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发表时间：
2012-03
影响因子：
--
通讯作者：
Rosenzweig, Holly L.
中科院分区：
文献类型：
--
作者：
Kezic, Jelena M.;Davey, Michael P.;Glant, Tibor T.;Rosenbaum, James T.;Rosenzweig, Holly L.
脊柱关节病（如强直性脊柱炎）是多系统炎性疾病，其经常导致葡萄膜炎或眼内炎症。尽管葡萄膜炎与关节炎共同发生，但对于眼睛对炎症的易感性还没有解释。使用一种创新的活体视频显微镜方法，我们发现在软骨蛋白聚糖（PG）免疫的小鼠中葡萄膜炎与轴向和外周关节炎症共存。在这里，我们阐明葡萄膜炎的特点，并测试IFNγ缺乏对眼睛与关节和脊柱的影响。雌性、TCR-Tg或IFNγ敲除与TCR-Tg杂交的小鼠用PG免疫。通过活体视频显微镜和组织学评估葡萄膜炎。评估关节炎和脊柱炎的临床和组织病理学严重程度。通过全身近红外成像评估脊柱内的骨重建过程。免疫印迹和免疫荧光染色用于检查PG和ADAMTS-5的表达沿着葡萄膜炎眼的细胞组成的检查。PG新表位与聚集蛋白聚糖酶ADAMTS-5一起沿着存在于眼睛中，因为它们是关节。前葡萄膜炎的发展是对PG免疫的反应。细胞浸润主要由中性粒细胞和嗜酸性粒细胞组成。出乎意料的是，IFNγ缺乏显著加重葡萄膜炎，同时改善关节和脊柱疾病，表明驱动眼部疾病与关节和脊柱疾病的不同机制。这是第一次详细描述的鼠科疾病模型，其中葡萄膜炎符合关节炎和脊柱炎。我们的观察提供了很好的机会，了解一个相对常见但知之甚少的疾病的发病机制。
The spondyloarthropathies (such as ankylosing spondylitis) are multi-system inflammatory diseases that frequently result in uveitis, or intra-ocular eye inflammation. Despite the common co-occurrence of uveitis with arthritis, there has been no explanation for the eye’s susceptibility to inflammation. Using an innovative intravital videomicroscopic approach, we discovered the co-existence of uveitis with axial and peripheral joint inflammation in mice immunized with cartilage proteoglycan (PG). Here, we elucidate the characteristics of uveitis and test the impact of IFNγ deficiency on the eye versus the joint and spine. Female, TCR-Tg or IFNγ knock-out crossed to TCR-Tg mice were immunized with PG. Uveitis was assessed by intravital videomicroscopy and histology. The clinical and histopathologic severity of arthritis and spondylitis were evaluated. Bone remodeling process within the spine was assessed by whole-body NIR imaging. Immunoblotting and immunofluorescence staining were used to examine expression of PG and ADAMTS-5 along with examination of the cellular composition of uveitic eyes. PG neo-epitopes along with the aggrecanase, ADAMTS-5, are present in the eye as they are the joint. Anterior uveitis develops in response to PG immunization. The cellular infiltrate consists mainly of neutrophils and eosinophils. Unexpectedly, IFNγ deficiency markedly exacerbates uveitis while ameliorating joint and spine disease, indicating divergent mechanisms that drive diseases in the eye versus joints and spine. This is the first detailed description of a murine disease model wherein uveitis coincides with arthritis and spondylitis. Our observations provide great opportunity to understand the pathogenesis of a relatively common but poorly understood disease.
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影响因子：
4.4
作者：
Doodes, Paul D.;Cao, Yanxia;Hamel, Keith M.;Wang, Yumei;Farkas, Balint;Iwakura, Yoichiro;Finnegan, Alison
通讯作者：
Finnegan, Alison
影响因子：
2.2
作者：
Becker, MD;Nobiling, R;Rosenbaum, JT
通讯作者：
Rosenbaum, JT
DOI：
10.4049/jimmunol.0902907
发表时间：
2010-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Doodes PD;Cao Y;Hamel KM;Wang Y;Rodeghero RL;Mikecz K;Glant TT;Iwakura Y;Finnegan A
通讯作者：
Finnegan A
影响因子：
--
作者：
Berlo, Suzanne E.;Guichelaar, Teun;Glant, Tibor T.
通讯作者：
Glant, Tibor T.
影响因子：
--
作者：
MIKECZ, K;GLANT, TT
通讯作者：
GLANT, TT