IL-27 Regulated CD4+IL-10+T Cells in Experimental Sjogren Syndrome
IL-27 Regulated CD4+IL-10+T Cells in Experimental Sjogren Syndrome
复制标题
实验性干燥综合征中 IL-27 调节的 CD4( )IL-10( )T 细胞
DOI：
10.3389/fimmu.2020.01699
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发表时间：
2020-08-11
影响因子：
7.3
通讯作者：
Yao, Genhong
中科院分区：
文献类型：
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作者：
Qi, Jingjing;Zhang, Zhuoya;Yao, Genhong
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IL-10的CD 4（+）T细胞的产生，其特征在于产生免疫抑制细胞因子IL-10。然而，IL-27是否通过调节CD 4（+）IL-10（+）T细胞参与干燥综合征（SS）的病理过程尚不清楚。本研究旨在探讨IL-27和CD 4（+）IL-10（+）T细胞在SS发病机制中的作用。产生IL-27基因敲除的非肥胖糖尿病（IL-27（-/-）NOD）小鼠并注射外源性IL-27。在NOD小鼠中进行IL-27的外源性注射和用抗IL-27抗体中和IL-27。观察颌下腺、泪腺、肺组织病理学改变、唾液流率及CD 4 + IL-10 + T细胞百分率。用IL-27免疫C57 L/B6小鼠，检测CD 4（+）IL-10（+）T细胞的比例，体外培养C57 L/B6小鼠脾脏幼稚T细胞，诱导CD 4（+）IL-10（+）T细胞分化。此外，在健康对照和SS患者中测定IL-27、IL-10和CD 4（+）IL-10（+）T细胞。结果表明，IL-27（-/-）NOD小鼠的病情较对照组严重，CD 4（+）IL-10（+）T细胞水平较对照组低。IL-27在体内和体外均能显著促进CD 4（+）IL-10（+）T细胞的生成和分化。与SS样小鼠中的发现一致，SS患者显示出较低水平的IL-27、IL-10和CD 4（+）IL-10（+）T细胞。我们的研究结果表明，IL-27缺乏通过调节CD 4（+）IL-10（+）T细胞加重SS。靶向IL-27和CD 4（+）IL-10（+）T细胞可能是治疗SS患者的一种新疗法。
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 Sjogren syndrome (SS) through regulating CD4(+)IL-10(+)T cells remains unknown. Here we aimed to explore the potential role of IL-27 and CD4(+)IL-10(+)T cells in the pathogenesis of SS. The IL-27 gene knockout non-obese diabetic (Il-27(-/-)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 CD4(+)IL-10(+)T cells were determined. And, ovalbumin-immunized C57L/B6 mice were injected with IL-27 to detect the percentage of CD4(+)IL-10(+)T cells.In vitro, splenic naive T cells from C57L/B6 mice were cultured with IL-27 for 4 days to induce the differentiation of CD4(+)IL-10(+)T cells. In addition, IL-27, IL-10, and CD4(+)IL-10(+)T cells were determined in health control and SS patients. The results showed thatIl-27(-/-)NOD mice had more severe disease and lower level of CD4(+)IL-10(+)T cells than control mice. And IL-27 promoted the generation and differentiation of CD4(+)IL-10(+)T cellsin vivoandin vitrosignificantly. In agreement with the findings in the SS-like mice, patients with SS showed lower levels of IL-27, IL-10, and CD4(+)IL-10(+)T cells. Our findings indicated that IL-27 deficiency aggravated SS by regulating CD4(+)IL-10(+)T cells. Targeting IL-27 and CD4(+)IL-10(+)T cells may be a novel therapy for patients with SS.