Chen Ying, Li Chao, Lu Yiping, Zhuang Huiying, Gu Weijia, Liu Bo, Liu Fangwei, Sun Jinkai, Yan Bo, Weng Dong, Chen Jie
Division of Pneumoconiosis, School of Public Health, China Medical University , Shenyang , China.
Department of Respiratory Medicine, Shenyang No. 9 Hospital , Shenyang , China.
Front Immunol. 2017 Feb 13;8:110. doi: 10.3389/fimmu.2017.00110. eCollection 2017.
Silicosis is characterized by chronic lung inflammation and fibrosis, which are extremely harmful to human health. The pathogenesis of silicosis involves uncontrolled immune processes. Evidence supports that regulatory B cells (Bregs) produce negative regulatory cytokines, such as IL-10, which can negatively regulate immune responses in inflammation and autoimmune diseases. Our previous study found that IL-10-producing B cells were involved in the development of silica-induced lung inflammation and fibrosis of mice. However, little is known about the role of Bregs in silicosis patients (SP). In this study, we found that serum concentrations of IL-10 were significantly increased in SP by using protein array screening. We further determined that the frequency of IL-10-producing CD1dCD5 Bregs, not IL-10-producing non-B lymphocytes, was significantly higher in SP compared to subjects under surveillance (SS) and healthy workers (HW) by flow cytometry. We also found that regulatory T cells (Tregs) and Th2 cytokines (IL-4, IL-5, and IL-13) were significantly increased in SP. Th1 cytokines (IFN-γ, IL-2, and IL-12) and inflammatory cytokines (IL-1β, IL-6, and TNF-α) were not significantly different between SP, SS, and HW. Our study indicated that IL-10-producing CD1dCD5 Bregs might maintain Tregs and regulate Th1/Th2 polarization in SP, suggesting that IL-10-producing Bregs may play a critical role in modulating immune homeostasis in SP.
矽肺的特征是慢性肺部炎症和纤维化，这对人类健康极其有害。矽肺的发病机制涉及不受控制的免疫过程。有证据表明，调节性B细胞（Bregs）产生负调节细胞因子，如IL-10，其可在炎症和自身免疫性疾病中负调节免疫反应。我们之前的研究发现，产生IL-10的B细胞参与了二氧化硅诱导的小鼠肺部炎症和纤维化的发展。然而，关于Bregs在矽肺患者（SP）中的作用知之甚少。在本研究中，我们通过蛋白质阵列筛选发现SP患者血清中IL-10浓度显著升高。我们进一步通过流式细胞术确定，与受监测对象（SS）和健康工人（HW）相比，SP患者中产生IL-10的CD1dCD5 Bregs而非产生IL-10的非B淋巴细胞的频率显著更高。我们还发现，SP患者中调节性T细胞（Tregs）和Th2细胞因子（IL-4、IL-5和IL-13）显著增加。SP、SS和HW之间的Th1细胞因子（IFN-γ、IL-2和IL-12）和炎性细胞因子（IL-1β、IL-6和TNF-α）无显著差异。我们的研究表明，产生IL-10的CD1dCD5 Bregs可能维持Tregs并调节SP患者的Th1/Th2极化，这表明产生IL-10的Bregs可能在调节SP患者的免疫稳态中起关键作用。
