Department of Clinical Immunology, Institute of Clinical Laboratory Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, No. 1 Xincheng Road, Dongguan, 523808, China.
Molecular Diagnostic Center, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, 511518, China.
Sci Rep. 2020 Aug 6;10(1):13212. doi: 10.1038/s41598-020-69984-y.
IL-35 is an anti-inflammatory cytokine and is thought to be produced by regulatory T (Treg) cells. A previous study found that IL-35 was upregulated in the serum of patients with active tuberculosis (ATB), and IL-35-producing B cells infiltrated to tuberculous granuloma of patients with ATB. Purified B cells from such patients generated more IL-35 after stimulation by antigens of Mycobacterium tuberculosis and secreted more IL-10. However, the function and the underlying mechanisms of IL-35-producing B cells in TB progression have not been investigated. The present study found that the expression of mRNA of IL-35 subsets Ebi3 and p35 was elevated in mononuclear cells from peripheral blood, spleen, bone marrow, and lung tissue in a mouse model infected with Mycobacterium bovis BCG, as tested by real-time polymerase chain reaction. Accordingly, the flow cytometry analysis showed that the counts of a subset of IL-35 B cells were elevated in the circulating blood and in the spleen, bone marrow, and lung tissue in BCG-infected mice, whereas anti-TB therapy reduced IL-35-producing B cells. Interestingly, BCG infection could drive the infiltration of IL-35-producing B cells into the lung tissue, and the elevated counts of IL-35-producing B cells positively correlated with the bacterial load in the lungs. Importantly, the injection of exogenous IL-35 stimulated the elevation in the counts of IL-35-producing B cells and was associated with the downregulation of Th1/Th17 and upregulation of Foxp3Treg.The study showed that a subset of IL-35-producing B cells might take part in the downregulation of immune response in mycobacterial infection.
白细胞介素 35（IL-35）是一种抗炎细胞因子，被认为是由调节性 T（Treg）细胞产生的。先前的研究发现，IL-35 在活动性肺结核（ATB）患者的血清中上调，并且 IL-35 产生的 B 细胞浸润到 ATB 患者的结核肉芽肿中。来自这些患者的纯化 B 细胞在受到结核分枝杆菌抗原刺激后产生更多的 IL-35，并分泌更多的 IL-10。然而，IL-35 产生的 B 细胞在结核病进展中的功能和潜在机制尚未得到研究。本研究发现，实时聚合酶链反应检测到，在感染牛分枝杆菌卡介苗（BCG）的小鼠模型的外周血、脾脏、骨髓和肺组织的单核细胞中，白细胞介素 35 亚群 Ebi3 和 p35 的 mRNA 表达升高。相应地，流式细胞术分析显示，BCG 感染小鼠的循环血液和脾脏、骨髓和肺组织中 IL-35 B 细胞亚群的计数升高，而抗结核治疗则减少了 IL-35 产生的 B 细胞。有趣的是，BCG 感染可促使 IL-35 产生的 B 细胞浸润到肺组织中，并且 IL-35 产生的 B 细胞计数的升高与肺部细菌负荷呈正相关。重要的是，外源性 IL-35 的注射刺激了 IL-35 产生的 B 细胞计数的升高，并与 Th1/Th17 的下调和 Foxp3Treg 的上调相关。该研究表明，IL-35 产生的 B 细胞亚群可能参与了分枝杆菌感染中免疫反应的下调。
