The IL-23/IL-17 axis is involved in inflammatory diseases including arthritis and psoriasis. However, the response to IL-23 or IL-17 inhibitors is different depending on the disease. The aim was to compare the effects of interactions between immune and stromal cells on the IL-23 axis to understand these differences. Peripheral blood mononuclear cells were co-cultured with RA synoviocytes or Pso skin fibroblasts, with or without phytohemagglutinin, IL-23, or anti-IL-23 antibody. Production of IL-6, IL-1β, IL-23, IL-17, IL-12, and IFNγ was measured by ELISA. IL-23 and cytokine receptor gene expression (IL-17RA, IL-17RC, IL-12Rβ1, IL-12Rβ2, and IL-23R) was analyzed by RT-qPCR. IL-12Rβ1 and IL-23R subunits were analyzed by flow cytometry. The production of IL-6, IL-1β, IL-17, IL-12, and IFNγ with synoviocytes or skin fibroblasts was rather similar, and cell interactions with immune cells increased their production, specifically that of IL-17. A major difference was observed for IL-23. Interactions with synoviocytes but not with skin fibroblasts decreased IL-23 secretion while mRNA level was increased, mainly with synoviocytes, reflecting a major consumption difference. IL-23 addition had only one effect, the increase of IL-17 secretion. Cell activation induced similar effects on cytokine receptor gene expression in co-cultures with synoviocytes or skin fibroblasts. The key difference was the cell interaction effects depending on the stromal cell origin. Interactions with synoviocytes increased the expression of both IL-23 receptor subunits at mRNA levels and IL-23R at the surface expression level while interactions with skin fibroblasts decreased their expression at the mRNA level and had no effect at the surface expression level. Interactions between immune and stromal cells are crucial in cytokine production and their receptor expression. The origin of stromal cells had a major influence on the production of IL-23 and its receptor expression. Such differences may explain part of the heterogeneity in treatment response.

中文翻译：

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在细胞与免疫细胞的相互作用过程中，滑膜细胞和皮肤成纤维细胞对 IL-23 的产生和 IL-23 受体的表达表现出相反的影响

IL-23/IL-17 轴参与炎症性疾病，包括关节炎和牛皮癣。然而，对 IL-23 或 IL-17 抑制剂的反应因疾病而异。目的是比较免疫细胞和基质细胞之间相互作用对 IL-23 轴的影响，以了解这些差异。外周血单个核细胞与 RA 滑膜细胞或 Pso 皮肤成纤维细胞共培养，有或没有植物血凝素、IL-23 或抗 IL-23 抗体。通过ELISA测量IL-6、IL-1β、IL-23、IL-17、IL-12和IFNγ的产生。通过 RT-qPCR 分析 IL-23 和细胞因子受体基因表达（IL-17RA、IL-17RC、IL-12Rβ1、IL-12Rβ2 和 IL-23R）。通过流式细胞术分析IL-12Rβ1和IL-23R亚基。IL-6、IL-1β、IL-17、IL-12 和 IFNγ 与滑膜细胞或皮肤成纤维细胞的产生相当相似，并且细胞与免疫细胞的相互作用增加了它们的产生，特别是IL-17的产生。观察到 IL-23 的主要差异。与滑膜细胞但不与皮肤成纤维细胞的相互作用减少了 IL-23 的分泌，而 mRNA 水平增加，主要与滑膜细胞，反映了主要的消耗差异。IL-23 的添加只有一个作用，即增加 IL-17 的分泌。在与滑膜细胞或皮肤成纤维细胞的共培养物中，细胞活化对细胞因子受体基因表达产生了类似的影响。关键区别在于取决于基质细胞来源的细胞相互作用效应。与滑膜细胞的相互作用增加了 mRNA 水平的 IL-23 受体亚基和表面表达水平的 IL-23R 的表达，而与皮肤成纤维细胞的相互作用降低了它们在 mRNA 水平的表达，并且在表面表达水平没有影响。免疫细胞和基质细胞之间的相互作用对细胞因子的产生及其受体表达至关重要。基质细胞的来源对 IL-23 的产生及其受体表达有重大影响。这种差异可以解释治疗反应的部分异质性。