Epratuzumab inhibits the production of the proinflammatory cytokines IL-6 and TNF-α, but not the regulatory cytokine IL-10, by B cells from healthy donors and SLE patients.
Epratuzumab inhibits the production of the proinflammatory cytokines IL-6 and TNF-α, but not the regulatory cytokine IL-10, by B cells from healthy donors and SLE patients.
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DOI：
10.1186/s13075-015-0686-2
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发表时间：
2015-07-17
影响因子：
4.9
通讯作者：
Dörner T
中科院分区：
文献类型：
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作者：
Fleischer V;Sieber J;Fleischer SJ;Shock A;Heine G;Daridon C;Dörner T
B细胞产生的细胞因子被认为在自身免疫性疾病中起着重要作用。Epratuzumab靶向CD22已被证明可以抑制B细胞中B细胞受体(BCR)下游信号的磷酸化。已有研究表明，与CD22相关的其他唾液粘附素分子具有免疫调节功能；因此，在本研究中，我们探讨了epratuzumab对系统性红斑狼疮(SLE)患者和健康献血者(HD)B细胞产生关键细胞因子的作用。外周血B细胞在有或没有Toll样受体9(TLR9)刺激的情况下，在有或没有epratuzumab的情况下被BCR纯化和激活。分析SLE和HD患者外周血中B细胞产生细胞因子IL-6、肿瘤坏死因子-α和IL-10的情况，以及IL-10+B细胞的诱导情况。Epratuzumab可抑制抗bcr抗体和bcr和/或TLR9激活的HD和SLE患者B细胞分泌促炎细胞因子Tf-α和IL-6。Epratuzumab在上述两种刺激条件下均不影响B细胞产生IL-10。Epratuzumab始终不影响培养中产生IL-10的B细胞的诱导。Epratuzumab通过靶向CD22，在体外能够抑制B细胞产生促炎细胞因子IL-6和肿瘤坏死因子α，而不是IL-10。这些数据表明，靶向CD22改变了促炎细胞因子(肿瘤坏死因子-α，IL-6)和调节性细胞因子IL-10之间的平衡，这是另一种B细胞效应机制。
Cytokines produced by B cells are believed to play important roles in autoimmune diseases. CD22 targeting by epratuzumab has been demonstrated to inhibit phosphorylation of B cell receptor (BCR) downstream signaling in B cells. It has been shown that other sialoadhesin molecules related to CD22 have immunoregulatory functions; therefore, in the present study, we addressed the role of epratuzumab on the production of key cytokines by B cells of patients with systemic lupus erythematosus (SLE) and of healthy donors (HD). Peripheral blood B cells were purified and activated by BCR with or without Toll-like receptor 9 (TLR9) stimulation in the presence or absence of epratuzumab. Cytokine production by B cells (interleukin [IL]-6, tumor necrosis factor [TNF]-α and IL-10) in the supernatant and the induction of IL-10+ B cells from patients with SLE and HD were analyzed. The secretion of the proinflammatory cytokines TNF-α and IL-6 by anti-BCR and BCR- and/or TLR9-activated B cells from HD and patients with SLE was inhibited by epratuzumab. In contrast, the production of IL-10 by B cells was not affected by epratuzumab under either stimulation condition. Consistently, the induction of IL-10–producing B cells in culture was not affected by epratuzumab. Epratuzumab, by targeting CD22, was able to inhibit the production of the proinflammatory cytokines IL-6 and TNF-α by B cells, in contrast to IL-10, in vitro. These data suggest that targeting CD22 alters the balance between proinflammatory cytokines (TNF-α, IL-6) and the regulatory cytokine IL-10 as another B cell effector mechanism.