Role of DAF in protecting against T-cell autoreactivity that leads to experimental autoimmune uveitis.
Role of DAF in protecting against T-cell autoreactivity that leads to experimental autoimmune uveitis.
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DAF 在防止导致实验性自身免疫性葡萄膜炎的 T 细胞自身反应中的作用。
DOI：
10.1167/iovs.08-3264
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发表时间：
2009-08
影响因子：
4.4
通讯作者：
Lin F
中科院分区：
文献类型：
--
作者：
An F;Li Q;Tu Z;Bu H;Chan CC;Caspi RR;Lin F
目的探讨衰变加速因子（decay-accelerating factor，EAU）在实验性自身免疫性葡萄膜炎（experimental autoimmune uveitis，EAU）发病机制中的作用。在野生型（WT）和Daf 1 −/−小鼠中诱导EAU，并比较其疾病严重程度、IRBP特异性Th 1/Th 17应答和细胞因子表达谱。在用可溶性小鼠EAU蛋白治疗的功效的测试中，在疾病易感的B10.RIII小鼠中诱导EAU，并且每隔一天用0.5mg可溶性EAU蛋白或等体积的PBS IP治疗它们。14天后比较视网膜组织学和IRBP特异性T细胞反应。EAU发病率和组织病理学评分在Daf 1 −/−小鼠中均显著更高。有>10倍的单核细胞流入视网膜，伴有严重的血管炎病变、视网膜折叠和感光细胞层破坏。在EAU Daf 1 −/−小鼠中，针对IRBP的Th 1和Th 17应答分别增加了5至7倍和3至4倍，并且它们表达的GM-CSF、IL-2、IL-3和IFN-γ水平显著升高。与接受PBS治疗的小鼠相比，接受可溶性Th 1蛋白治疗的WT B10.RIII小鼠表现出降低的IRBP特异性Th 1/Th 17应答，并保护其免受视网膜损伤。EAU患者IRBP特异性Th 1和Th 17应答及疾病严重程度与EAU患者有显著性差异。系统性上调视网膜抗原水平可用于抑制视网膜抗原特异性自身免疫以治疗自身免疫性后葡萄膜炎。
To investigate the role of decay-accelerating factor (DAF), a cell surface complement regulator that recently has been linked to T-cell responses and autoimmunity in the pathogenesis of experimental autoimmune uveitis (EAU). EAU was induced in wild-type (WT) and Daf1−/− mice, and their disease severities, IRBP specific Th1/Th17 responses, and cytokine expression profiles were compared. In a test of the efficacy of treatment with soluble mouse DAF protein, EAU was induced in disease-susceptible B10.RIII mice, and they were treated with 0.5 mg soluble DAF protein or equal volume of PBS IP every other day. Retinal histology and IRBP-specific T-cell responses were compared after 14 days. Both EAU incidence and histopathology scores were significantly greater in Daf1−/− mice. There was a >10-fold greater mononuclear cell influx into the retina together with severe vasculitic lesions, retinal folding, and photoreceptor cell layer destruction. There were 5- to 7-fold greater Th1 and 3- to 4-fold greater Th17 responses against IRBP in Daf1−/− mice with EAU, and they expressed significantly elevated levels of GM-CSF, IL-2, IL-3, and IFN-γ. WT B10.RIII mice that received soluble DAF protein treatments exhibited decreased IRBP-specific Th1/Th17 responses and were protected from retinal injury compared with the mice that received PBS treatments. DAF significantly influences IRBP-specific Th1 and Th17 responses and disease severity in EAU. Systemic upregulation of DAF levels could be used to suppress retinal antigen(s)–specific autoimmunity to treat autoimmune posterior uveitis.
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DOI：
10.1084/jem.20041967
发表时间：
2005-05-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Heeger PS;Lalli PN;Lin F;Valujskikh A;Liu J;Muqim N;Xu Y;Medof ME
通讯作者：
Medof ME
影响因子：
4.4
作者：
Liu, Jinbo;Lin, Feng;Medof, M. Edward
通讯作者：
Medof, M. Edward
影响因子：
3.4
作者：
Kohno, Hideo;Sakai, Tsutomu;Kitahara, Kenji
通讯作者：
Kitahara, Kenji
影响因子：
12.8
作者：
CHAN, CC;CASPI, RR;NUSSENBLATT, RB
通讯作者：
NUSSENBLATT, RB
影响因子：
20.3
作者：
Lalli, Peter N.;Strainic, Michael G.;Heeger, Peter S.
通讯作者：
Heeger, Peter S.