Zhang Xiao, Sun Yi, He Caiyun, Qiu Xiaofen, Zhou Dalei, Ye Zulu, Long Yakang, Tang Tao, Su Xuan, Ma Jiangjun
State Key Laboratory of Oncology in South China, Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Pediatric, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Microbiol Immunol. 2018 Apr;62(4):281-290. doi: 10.1111/1348-0421.12583. Epub 2018 Apr 18.
We aimed to assess the immunoregulatory effects of IFN-β in patients with tuberculous pleurisy. IFN-β, IFN-γ and IL-17 expression levels were detected, and correlations among these factors in different culture groups were analyzed. Pleural fluid mononuclear cells (PFMC) from tuberculous pleural effusions, but not peripheral blood mononuclear cells (PBMC) from healthy donors, spontaneously expressed IFN-β, IL-17 and IFN-γ. Moreover, exogenous IFN-β significantly inhibited the expression of IL-17 in PFMC. By contrast, IFN-β simultaneously enhanced the levels of IFN-γ. To further investigate the regulation of IL-17 and IFN-γ by endogenous IFN-β, an IFN-β neutralizing antibody was simultaneously added to bacillus Calmette-Guérin (BCG)-stimulated PFMC. IL-17 expression was significantly increased, but IFN-γ production was markedly decreased in the experimental group supplemented with the IFN-β neutralizing antibody. Simultaneously, IL-17 production was remarkably increased in the experimental group supplemented with the IFN-γ neutralizing antibody. Taken together, in our study, we first found that freshly isolated PFMC, but not PBMC from healthy donors, spontaneously expressed IFN-β, IL-17 and IFN-γ in vivo. Moreover, IFN-β suppressed IL-17 expression and increased IFN-γ production. Furthermore, both IFN-β and IFN-γ down-regulated IL-17 expression. These observations suggest that caution is required when basing anti-tuberculosis treatment on the inhibition of IFN-β signaling.
我们旨在评估干扰素-β（IFN-β）对结核性胸膜炎患者的免疫调节作用。检测了IFN-β、干扰素-γ（IFN-γ）和白细胞介素-17（IL-17）的表达水平，并分析了不同培养组中这些因子之间的相关性。结核性胸腔积液中的胸腔积液单核细胞（PFMC），而非健康供者的外周血单核细胞（PBMC），可自发表达IFN-β、IL-17和IFN-γ。此外，外源性IFN-β显著抑制PFMC中IL-17的表达。相比之下，IFN-β同时提高了IFN-γ的水平。为进一步研究内源性IFN-β对IL-17和IFN-γ的调节作用，将IFN-β中和抗体同时添加到卡介苗（BCG）刺激的PFMC中。在添加IFN-β中和抗体的实验组中，IL-17表达显著增加，但IFN-γ产生明显减少。同时，在添加IFN-γ中和抗体的实验组中，IL-17产生显著增加。综上所述，在我们的研究中，我们首次发现，新鲜分离的PFMC而非健康供者的PBMC在体内可自发表达IFN-β、IL-17和IFN-γ。此外，IFN-β抑制IL-17表达并增加IFN-γ产生。此外，IFN-β和IFN-γ均下调IL-17表达。这些观察结果表明，在基于抑制IFN-β信号进行抗结核治疗时需要谨慎。
