Yin Cheng, Cai Xu-Bing, Wang Hui-Juan, Gu Bing-Jie, Yang Xiao-Fan, Zhang Rong, Ji Xiao-Hui
Department of Immunology, Basic Medical School, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Red Cross Blood Center, Nanjing, Jiangsu 210003, China.
J Biomed Res. 2018 Mar 26;32(2):113-122. doi: 10.7555/JBR.27.20130046.
Systemic lupus erythematosus (SLE) is a typical autoimmune disease. Lymphotoxin β receptor (LTβR) signaling plays an important role in autoimmune inflammations. LTβR-Ig fusion protein, LTβR blocking agent, has been used to treat SLE, while its mechanism remains to be fully elucidated. In this study, to investigate the expression of LTβR in the T cells of SLE patients and its roles in the pathogenesis of SLE, we isolated the peripheral blood T cells of SLE patients and normal controls to detect expression of LTβR by flow cytometry and RNA assay. T cells were also stimulated with LIGHT, a ligand of LTβR, and then detected for their LTβR expressions and apoptosis by flow cytometry. Also, their expressions of inflammatory factors and receptors were determined by RNA assay. The results showed that LTβR positive cells were 22.75%±6.98% in CD3 cells of SLE patients, while there were almost no LTβR positive cells in CD3 cells of normal persons. Moreover, LTβR expression was remarkably higher in CD3, CD4 and CD8 positive T cells of active SLE patients than non/low active patients (all <0.05), and positively correlated with increased Ig level, decreased complement level and renal damage. Moreover, the stimulation of SLE T cells with LIGHT promoted higher expression of LTβR, IL-23R and IL-17A, and apoptosis of T cells. In conclusion, we demonstrated a high expression of LTβR in the T cells of SLE patients which may be associated with pathogenesis of SLE.
系统性红斑狼疮（SLE）是一种典型的自身免疫性疾病。淋巴毒素β受体（LTβR）信号传导在自身免疫性炎症中起重要作用。LTβR-Ig融合蛋白，即LTβR阻断剂，已被用于治疗SLE，但其机制仍有待充分阐明。在本研究中，为了探讨SLE患者T细胞中LTβR的表达及其在SLE发病机制中的作用，我们分离了SLE患者和正常对照者的外周血T细胞，通过流式细胞术和RNA检测来检测LTβR的表达。还用LTβR的配体LIGHT刺激T细胞，然后通过流式细胞术检测其LTβR表达和细胞凋亡。此外，通过RNA检测确定其炎症因子和受体的表达。结果显示，SLE患者CD3细胞中LTβR阳性细胞为22.75%±6.98%，而正常人CD3细胞中几乎没有LTβR阳性细胞。此外，活动期SLE患者CD3、CD4和CD8阳性T细胞中LTβR表达明显高于非/低活动期患者（均<0.05），且与Ig水平升高、补体水平降低和肾脏损害呈正相关。此外，用LIGHT刺激SLE T细胞可促进LTβR、IL-23R和IL-17A的更高表达以及T细胞凋亡。总之，我们证明了SLE患者T细胞中LTβR的高表达可能与SLE的发病机制有关。
