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The protective function of invariant natural killer T cells in the relapse of experimental autoimmune uveoretinitis
Experimental Eye Research ( IF 3.0 ) Pub Date : 2020-12-19 , DOI: 10.1016/j.exer.2020.108406
Natsumi Tajiri , Taiki Kato , Masashi Satoh , Misao Iizuka , Masaru Taniguchi , Nobuyoshi Kitaichi , Kazuya Iwabuchi

Experimental autoimmune uveoretinitis (EAU) in mice provides a useful platform to study the pathogenesis and experimental therapeutics of human uveitis. One often used EAU model employs C57BL/6 (B6) mice sensitized with a peptide residue having 1 to 20 amino acids of human interphotoreceptor retinoid binding protein (hIRBP1-20). The model using the B6 background has permitted a liberal use of genetically engineered strains and has provided insights for understanding uveoretinitis. However, this is usually acute/monophasic and does not represent human uveoretinitis that is characterized as a chronic/recurrent disease. Several chronic/recurrent EAU models have been developed; of these, we employed administration of staphylococcal enterotoxin B (SEB) for relapse in the present study, and found that recurrence was induced at day 24 after primary immunization, which is thought to be the convalescent phase. We reported the activation of invariant natural killer T (iNKT)-cells upon primary immunization of the EAU model mice with the ligand RCAI-56, which was found to mitigate the disease in our previous study. Here, we first attempted to ameliorate EAU in the relapse model using a preventive regimen by activating iNKT cells at the same time relapse induction (day 24) or in a regimen after 3 days of relapse induction (day 27). The preventive as well as post-inductive regimens were successful in reducing histopathological scores by inhibiting the Ag-specific Th17-biased response. Collectively, activation of iNKT cells may be useful to mitigate the relapse response of EAU induced with SEB.



中文翻译:

不变的自然杀伤性T细胞在实验性自身免疫性葡萄膜视网膜炎复发中的保护作用

小鼠实验性自身免疫性葡萄膜视网膜炎(EAU)为研究人葡萄膜炎的发病机理和实验疗法提供了有用的平台。一种经常使用的EAU模型使用C57BL / 6(B6)小鼠,该小鼠用具有1至20个氨基酸的人感光素类视黄醇结合蛋白(hIRBP 1-20)。使用B6背景的模型允许广泛使用基因工程菌株,并为了解葡萄膜视网膜炎提供了见识。但是,这通常是急性/单相的,并不代表以慢性/复发性疾病为特征的人葡萄膜视网膜炎。已经开发了几种慢性/复发性EAU模型。在这些研究中,我们在本研究中采用了葡萄球菌肠毒素B(SEB)的治疗方法,发现在初次免疫后的第24天诱导了复发,这被认为是恢复期。我们报道了用配体RCAI-56对EAU模型小鼠进行初次免疫后,不变自然杀伤T(iNKT)细胞的激活,这在我们先前的研究中被发现可以缓解这种疾病。这里,我们首先尝试通过预防性方案通过同时诱导复发(第24天)或诱导复发3天(第27天)的方案激活iNKT细胞来改善复发模型中的EAU。预防方案和诱导后方案均通过抑制Ag特异性的Th17偏向反应成功降低了组织病理学评分。总的来说,iNKT细胞的激活可能有助于减轻SEB诱导的EAU的复发反应。

更新日期:2021-01-10
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