Suppression of collagen-induced arthritis by natural killer T cell activation with OCK a sphingosine-truncated analog of α-galactosylceramide
Suppression of collagen-induced arthritis by natural killer T cell activation with OCK a sphingosine-truncated analog of α-galactosylceramide
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DOI：
10.1002/art.11489
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发表时间：
2004-01-01
影响因子：
--
通讯作者：
Miyake, S
中科院分区：
文献类型：
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作者：
Chiba, A;Oki, S;Miyake, S
客观的。 OCH 是一种具有截短鞘氨醇链的 α-半乳糖神经酰胺的合成类似物，可刺激自然杀伤 T (NKT) 细胞主要产生 Th2 细胞因子。因此，OCH可能是治疗Th1介导的自身免疫性疾病的潜在药物。本研究旨在评估 OCH 对小鼠胶原诱导性关节炎 (CIA) 的保护作用。方法。在 CIA 发作之前或之后，用 II 型胶原蛋白（CII）对小鼠进行免疫，并每周两次腹腔注射 OCH。对他们进行监测以评估 OCH 治疗对疾病严重程度的影响。通过酶联免疫吸附测定法测量抗 CII 抗体和细胞因子的产生。通过定量逆转录酶-聚合酶链反应测定细胞因子基因的表达。结果。 OCH 抑制野生型 C57BL/6 (B6) 小鼠的 CIA，但不抑制 NKT 缺陷小鼠的 CIA。 OCH 抑制了 SJL 小鼠的 CIA，这些小鼠容易患自身免疫性疾病，并且 NKT 细胞数量和功能缺乏，这与患有自身免疫性疾病的患者相似，即使在疾病已经发展之后也是如此。 OCH 赋予的疾病保护作用与其选择性诱导 NKT 细胞介导的 Th2 细胞因子产生以及促进胶原蛋白特异性 Th2 反应的能力相关。用单克隆抗体中和白细胞介素 4 (IL-4) 或 IL-10 消除了 OCH 的疾病保护作用，表明这些细胞因子的关键作用。结论。总而言之，我们的研究结果表明 OCH 具有作为类风湿性关节炎等自身免疫性疾病的治疗剂的可能性。
Objective. OCH, a synthetic analog of a-galactosylceramide with a truncated sphingosine chain, stimulates natural killer T (NKT) cells to produce predominantly Th2 cytokines. Thus, OCH may be a potential agent for the treatment of Th1-mediated autoimmune diseases. This study was designed to evaluate the protective effects of OCH on collagen-induced arthritis (CIA) in mice.Methods. Mice were immunized with type II collagen (CII) and injected intraperitoneally twice per week with OCH, before or after the onset of CIA. They were monitored to assess the effect of OCH treatment on the severity of disease. Anti-CII antibodies and cytokine production were measured by enzyme-linked immunosorbent assay. Expression of cytokine genes was determined by quantitative reverse transcriptase-polymerase chain reaction.Results. OCH inhibited CIA in wild-type C57BL/6 (B6) mice but not in NKT-deficient mice. OCH suppressed CIA in SJL mice, which are prone to autoimmune diseases and have a deficiency in the number and function of NKT cells which is similar to that in patients with autoimmune diseases, even after disease has already developed. Disease protection conferred by OCH correlated with its ability to selectively induce Th2 cytokine production mediated by NKT cells and to promote collagen-specific Th2 responses. Neutralization of interleukin-4 (IL-4) or IL-10 with monoclonal antibodies abolished disease protection by OCH, indicating a critical role for these cytokines.Conclusion. Taken together, our findings suggest that OCH holds possibilities as a therapeutic agent for autoimmune diseases such as rheumatoid arthritis.