Department of Immunology, School of Basic Medical, Zhengzhou University, Zhengzhou, China.
College of Veterinary Medicine, North West Agriculture and Forestry University, Zhengzhou, China.
Scand J Immunol. 2018 Jul;88(1):e12676. doi: 10.1111/sji.12676.
The thymus of a myasthenia gravis (MG) patient is often accompanied by and effected with follicular hyperplasia. Inflammatory cytokines in thymus induce the formation of germinal centres (GC). MG thymic inflammatory cytokines are predominantly secreted by stromal cells. Our previous studies revealed that the expression level of the Fra1 protein, which is a Fos member of the activator protein 1 transcription factors (AP-1), was higher in the MG thymus compared with that of the normal thymus. Based on that, we demonstrated that Fra1 was mainly expressed in medulla thymic epithelial cells (mTECs) and that the rate of Fra1 positive mTECs in the MG thymus was higher than normal. In vitro, we found that the expression of CCL-5, CCL-19 and CCL-21 could be regulated by Fra1 in mTEC and that IL-1β, IL-6, IL-8 and ICAM1 were downregulated in the Fra1 overexpression group and upregulated in the Fra1 knock-down group. Meanwhile, we detected that the expression levels of suppressor of cytokine signalling 3 (SOCS3) were significantly upregulated along with the overexpression of Fra1. Hence, we considered that the overexpression of Fra1 disrupted inflammatory cytokine secretion by mTEC in the MG thymus and that STAT3 and SOCS3 were strongly involved in this process.
重症肌无力（MG）患者的胸腺常伴有滤泡增生，并受其影响。胸腺中的炎症细胞因子诱导生发中心（GC）的形成。MG 胸腺炎症细胞因子主要由基质细胞分泌。我们之前的研究表明，激活蛋白 1（AP-1）转录因子中 Fos 成员 Fra1 蛋白的表达水平在 MG 胸腺中高于正常胸腺。基于这一点，我们证明 Fra1 主要在胸皮质上皮细胞（mTEC）中表达，并且 Fra1 阳性 mTEC 在 MG 胸腺中的比率高于正常。在体外，我们发现 Fra1 可调节 mTEC 中 CCL-5、CCL-19 和 CCL-21 的表达，并且 Fra1 过表达组中 IL-1β、IL-6、IL-8 和 ICAM1 的表达下调，而 Fra1 敲低组中则上调。同时，我们检测到 Fra1 过表达时细胞因子信号转导抑制因子 3（SOCS3）的表达水平显著上调。因此，我们认为 Fra1 的过表达破坏了 MG 胸腺中 mTEC 炎症细胞因子的分泌，STAT3 和 SOCS3 强烈参与了这一过程。
