Institut Cochin, Université Paris Descartes CNRS (UMR 8104), Paris, France.
Eur J Immunol. 2010 Feb;40(2):460-9. doi: 10.1002/eji.200939566.
Cytokines and CD4(+) Th cells play a crucial role in the pathogenesis of rheumatoid arthritis. Among the Th populations, Th-1 and Th-17 have been described as pathogenic in collagen-induced arthritis (CIA) whereas Th-2 and Treg were found to have protective effects. The objective of this study was to examine the affect of Natura-alpha, a newly developed cytokine regulator, on CIA and on Th cell development. Natura-alpha treatment was administered before or during arthritis induction. Anti-type II collagen antibodies and cytokine expression were evaluated by ELISA. Emergence of CD4(+)CD25(+)Foxp3(+) T cells was assessed by flow cytometry. Th-17 differentiation of naive CD4 T cells was assessed in cultures with anti-CD3 and anti-CD28. We showed that Natura-alpha both prevented and treated CIA. We further demonstrated that in vivo treatment with Natura-alpha inhibited IL-17 production and anti-type II collagen IgG development. We showed in vitro, using an APC-free system, that Natura-alpha acted directly on differentiating T cells and inhibiting the formation of Th-1 and Th-17 cells but did not affect Th-2 cells. Since Natura-alpha inhibits a large spectrum of important pathogenic factors in CIA, it may provide a new and powerful approach to the treatment of rheumatoid arthritis and other inflammatory diseases.
细胞因子和 CD4(+)Th 细胞在类风湿关节炎的发病机制中起着至关重要的作用。在 Th 细胞群体中，Th-1 和 Th-17 被描述为胶原诱导关节炎 (CIA) 中的致病性细胞，而 Th-2 和 Treg 被发现具有保护作用。本研究的目的是研究一种新开发的细胞因子调节剂 Natura-alpha 对 CIA 和 Th 细胞发育的影响。Natura-alpha 治疗在关节炎诱导前或期间进行。通过 ELISA 评估抗 II 型胶原抗体和细胞因子表达。通过流式细胞术评估 CD4(+)CD25(+)Foxp3(+)T 细胞的出现。通过抗 CD3 和抗 CD28 培养物评估幼稚 CD4 T 细胞的 Th-17 分化。我们表明 Natura-alpha 既可以预防又可以治疗 CIA。我们进一步证明，体内用 Natura-alpha 治疗可抑制 IL-17 产生和抗 II 型胶原 IgG 发育。我们在无 APC 的体外系统中表明，Natura-alpha 直接作用于分化的 T 细胞，抑制 Th-1 和 Th-17 细胞的形成，但不影响 Th-2 细胞。由于 Natura-alpha 抑制 CIA 中许多重要的致病性因素，它可能为治疗类风湿关节炎和其他炎症性疾病提供一种新的、强大的方法。
