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在实验性自身免疫性葡萄膜炎期间发现免疫调节因子程序性死亡1(PD-1)的组成性神经元表达。

Constitutive neuronal expression of the immune regulator, programmed death 1 (PD-1), identified during experimental autoimmune uveitis.

作者信息

Chen Ling, Pai Vicky, Levinson Ralph, Sharpe Arlene H, Freeman Gordon J, Braun Jonathan, Gordon Lynn K

机构信息

Department of Ophthalmology, Jules Stein Institute, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.

出版信息

Ocul Immunol Inflamm. 2009 Jan-Feb;17(1):47-55. doi: 10.1080/09273940802491884.

Abstract

PURPOSE

Programmed death-1 (PD-1) ligation downregulates active lymphocyte responses. The authors tested whether PD-1 or its ligands are expressed in the posterior segment during active intraocular inflammation.

METHODS

Experimental autoimmune uveitis (EAU) was induced using interphotoreceptor retinoid-binding protein (IRBP 161-180). Ocular inflammation was evaluated by histology and expression of PD-1 ligand tested by immunohistochemistry. PD-1 expression was evaluated by immunohistochemistry, RT-PCR, and Western immunoblotting.

RESULTS

Using immunohistochemistry, PD-1, but not its ligands, was constitutively expressed in retinal neurons of naive mouse retina. Both PD-1 and its ligands were observed, as expected, in sites of active inflammation.

CONCLUSIONS

PD-1 and its ligands were expressed in sites of active inflammation, in accordance with many other models of inflammatory disease. Surprisingly, PD-1, not previously described outside the immune system, was constitutively expressed in retinal neurons, raising the possibility that PD-1 signaling may be important for neuronal function in the absence of an inflammatory insult.

摘要

目的

程序性死亡因子1(PD-1)的连接可下调活跃淋巴细胞反应。作者检测了在活跃性眼内炎症期间,PD-1或其配体是否在后段表达。

方法

使用光感受器间类视黄醇结合蛋白(IRBP 161-180)诱导实验性自身免疫性葡萄膜炎(EAU)。通过组织学评估眼部炎症,并通过免疫组织化学检测PD-1配体的表达。通过免疫组织化学、逆转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹法评估PD-1的表达。

结果

使用免疫组织化学方法,PD-1而非其配体在未免疫小鼠视网膜的视网膜神经元中组成性表达。正如预期的那样,在活跃炎症部位观察到了PD-1及其配体。

结论

与许多其他炎症性疾病模型一致,PD-1及其配体在活跃炎症部位表达。令人惊讶的是,PD-1在免疫系统之外此前未被描述过,却在视网膜神经元中组成性表达,这增加了在没有炎症刺激的情况下,PD-1信号传导可能对神经元功能很重要的可能性。

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