Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Department of Immunology, College of Basic Medical Science, Dalian Medical University, Dalian, Liaoning, China.
Front Immunol. 2020 Aug 11;11:1699. doi: 10.3389/fimmu.2020.01699. eCollection 2020.
Interleukin 27 (IL-27) plays diverse immune regulatory roles in autoimmune disorders and promotes the generation of IL-10-producing CD4 T cells characterized by producing the immunosuppressive cytokine IL-10. However, whether IL-27 participates in pathological progress of Sjögren syndrome (SS) through regulating CD4IL-10 T cells remains unknown. Here we aimed to explore the potential role of IL-27 and CD4IL-10 T cells in the pathogenesis of SS. The IL-27 gene knockout non-obese diabetic (NOD) mice were generated and injected with exogenous IL-27. Exogenous injection of IL-27 and neutralization of IL-27 with anti-IL-27 antibody in NOD mice were performed. The histopathologic changes in submandibular glands, lacrimal glands and lung, salivary flow rate, and percentages of CD4IL-10 T cells were determined. And, ovalbumin-immunized C57L/B6 mice were injected with IL-27 to detect the percentage of CD4IL-10 T cells. , splenic naive T cells from C57L/B6 mice were cultured with IL-27 for 4 days to induce the differentiation of CD4IL-10 T cells. In addition, IL-27, IL-10, and CD4IL-10 T cells were determined in health control and SS patients. The results showed that NOD mice had more severe disease and lower level of CD4IL-10 T cells than control mice. And IL-27 promoted the generation and differentiation of CD4IL-10 T cells and significantly. In agreement with the findings in the SS-like mice, patients with SS showed lower levels of IL-27, IL-10, and CD4IL-10 T cells. Our findings indicated that IL-27 deficiency aggravated SS by regulating CD4IL-10 T cells. Targeting IL-27 and CD4IL-10 T cells may be a novel therapy for patients with SS.
白细胞介素 27（IL-27）在自身免疫性疾病中发挥多种免疫调节作用，并促进产生具有免疫抑制细胞因子 IL-10 的 IL-10 产生 CD4 T 细胞。然而，IL-27 是否通过调节 CD4IL-10 T 细胞参与干燥综合征（SS）的病理进程尚不清楚。在这里，我们旨在探讨 IL-27 和 CD4IL-10 T 细胞在 SS 发病机制中的潜在作用。生成 IL-27 基因敲除非肥胖型糖尿病（NOD）小鼠，并注射外源性 IL-27。在 NOD 小鼠中进行外源性 IL-27 注射和用抗 IL-27 抗体中和 IL-27。测定颌下腺、泪腺和肺的组织病理学变化、唾液流量和 CD4IL-10 T 细胞的百分比。并且，用 IL-27 注射卵清蛋白免疫的 C57L/B6 小鼠，以检测 CD4IL-10 T 细胞的百分比。从小鼠脾中分离出幼稚 T 细胞，用 IL-27 培养 4 天，诱导 CD4IL-10 T 细胞的分化。此外，还测定了健康对照者和 SS 患者的 IL-27、IL-10 和 CD4IL-10 T 细胞。结果表明，与对照小鼠相比，NOD 小鼠的疾病更严重，CD4IL-10 T 细胞水平更低。并且 IL-27 促进了 CD4IL-10 T 细胞的产生和分化。与 SS 样小鼠的发现一致，SS 患者的 IL-27、IL-10 和 CD4IL-10 T 细胞水平较低。我们的研究结果表明，IL-27 通过调节 CD4IL-10 T 细胞加重 SS。靶向 IL-27 和 CD4IL-10 T 细胞可能是 SS 患者的一种新疗法。
