The purpose of the present study was to broaden the knowledge and understanding of the effects of oclacitinib (OCL), a Janus kinase inhibitor, on T cells in the context of both the immune mechanisms underlying anti-inflammatory and anti-allergic properties of the drug and its safety. The results indicate that beneficial effects of OCL in the treatment of skin allergic diseases may be partially mediated by the inhibition of IL-4 production in CD4⁺ and CD8⁺ T cells. To a certain extent, the antiproliferative effect of OCL on CD8⁺ T cells may also contribute to its therapeutic effect. The study found that OCL does not affect the proliferation of CD4⁺ T cells or the number of IFN-γ- and IL-17-producing CD4⁺ and CD8⁺ T cells. Moreover, OCL was found to counteract the induction of type 1 regulatory T (Tr1) cells and to act as a strong inhibitor of IL-10 production in both CD4⁺ and CD8⁺ T cells. Thus, these results indicate that beneficial effects of OCL in the treatment of skin allergic diseases are not mediated through: (a) the abolishment of IFN-γ and IL-17-production in CD4⁺ and CD8⁺ T cells; (b) generation of Tr1 cells; (c) inhibition of CD4⁺ T cell proliferation; (d) induction of IL-10 production in CD4⁺ T cells. The results of this study strongly suggest that, with respect to the evaluated parameters, OCL exerts a suppressive effect on Th2- but not Th1-mediated immunity.

中文翻译：

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Oclacitinib 是一种 Janus 激酶抑制剂，可降低 IL-4- 和 IL-10-（但不包括 IFN-γ-）的频率，从而产生鼠 CD4+ 和 CD8+ T 细胞并抵消 1 型调节性 T 细胞的诱导


本研究的目的是在药物抗炎和抗过敏特性的免疫机制背景下，扩大对奥拉替尼 (OCL)（一种 Janus 激酶抑制剂）对 T 细胞影响的认识和理解及其安全性。结果表明，OCL 在治疗皮肤过敏性疾病中的有益作用可能部分是通过抑制 CD4 ⁺和 CD8 ⁺ T 细胞中 IL-4 的产生来介导的。在一定程度上，OCL对CD8 ⁺ T细胞的抗增殖作用也可能有助于其治疗效果。研究发现，OCL不会影响CD4 ⁺ T细胞的增殖或产生IFN-γ和IL-17的CD4 ⁺和CD8 ⁺ T细胞的数量。此外，OCL 被发现可以抵消 1 型调节性 T (Tr1) 细胞的诱导，并作为 CD4 ⁺和 CD8 ⁺ T 细胞中 IL-10 产生的强抑制剂。因此，这些结果表明 OCL 在治疗皮肤过敏性疾病中的有益作用不是通过以下介导的：(a) 消除 CD4 ⁺和 CD8 ⁺ T 细胞中 IFN-γ 和 IL-17 的产生； (b) Tr1细胞的产生； (c)抑制CD4 ⁺ T细胞增殖； (d)诱导CD4 ⁺ T细胞产生IL-10。这项研究的结果强烈表明，就评估参数而言，OCL 对 Th2 介导的免疫发挥抑制作用，但对 Th1 介导的免疫没有抑制作用。