Immunoregulatory role of ocular macrophages: The macrophages produce RANTES to suppress experimental autoimmune uveitis
Immunoregulatory role of ocular macrophages: The macrophages produce RANTES to suppress experimental autoimmune uveitis
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DOI：
10.4049/jimmunol.171.5.2652
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发表时间：
2003-09-01
影响因子：
4.4
通讯作者：
Ishibashi, T
中科院分区：
文献类型：
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作者：
Sonoda, KH;Sasa, Y;Ishibashi, T
小鼠实验性自身免疫性葡萄膜炎(EAU)是人类葡萄膜炎的一种模型。眼部浸润性巨噬细胞在EAU组织损伤的发生中起关键作用。事实上，发炎的眼睛实际上会产生几种趋化因子。本研究的目的是阐明眼部巨噬细胞衍生的趋化因子在EAU中的作用。用人视黄样受体结合蛋白多肽1-20免疫C57BL/6小鼠，根据眼底镜检(视网膜血管扩张和渗出物)和组织学检查，在多个时间点对EAU的严重程度进行评分。炎症反应高峰出现在眼部巨噬细胞开始渗入眼后1wk(第16天)。用磁珠富集或去除眼部浸润性细胞中的巨噬细胞，并用实时定量RT-PCR分析趋化因子mRNA的产生。我们发现只有眼部富含巨噬细胞的细胞才能产生RANTES，从而提示巨噬细胞来源的RANTES促进了眼部炎症。与我们的假设相反，体内特定抗体在第9天和第13天中和RANTES会加剧EAU。治疗后眼CD_4/CD_8 T细胞比值明显升高。因此，RANTES中和可能通过调节招募到眼睛的T细胞亚群的类型来加重EAU。总之，我们的数据为巨噬细胞和RANTES在眼部炎症发病机制中的免疫调节作用提供了洞察力。并非所有巨噬细胞衍生的趋化因子都会引起局部炎症，因为眼部巨噬细胞产生的RANTES似乎能抑制EAU。
Murine experimental autoimmune uveitis (EAU) is a model of human uveitis. Ocular-infiltrating macrophages play a crucial role in the generation of tissue damage in EAU. In fact, several chemokines are actually produced in the inflamed eye. The aim of this study was to elucidate the role of ocular macrophage-derived chemokines in EAU. C57BL/6 mice were immunized with human interphotoreceptor retinoid binding protein peptide 1-20, and the EAU severity was scored at multiple time points based on microscopic fundus observations (retinal vascular dilatation and exudates) and histological examinations. The peak inflammatory response was observed 1 wk (day 16) after the beginning of macrophage infiltration to the eye (day 9). Ocular-infiltrating cells were enriched or depleted of macrophages by magnetic beads And analyzed by real-time RT-PCR for chemokine mRNA production. We found that only the macrophage-enriched cells from the eye produced RANTES, and thus proposed that macrophage-derived RANTES facilitated the ocular inflammations. In contrast to our postulate, neutralization of RANTES by specific Ab in vivo on days 9 and 13 exacerbated EAU. We also found that the ratio of ocular CD4/CD8 T cells was markedly increased after treatment. As a result, RANTES neutralization might exacerbate EAU by modulating the type of T cell subsets recruited to the eye. In conclusion, our data provide insight into the immunoregulatory role of macrophages and RANTES in the pathogenesis of ocular inflammation. Not all macrophage-derived chemokines cause local inflammation, since RANTES produced by ocular macrophages appears to suppress EAU.