Pathological significance and regulatory mechanism of lymphotoxin β receptor overexpression in T cells of patients with systemic lupus erythematosus  

作　　者：Cheng Yin Xubing Cai Huijuan Wang Bingjie Gu Xiaofan Yang Rong Zhang Xiaohui Ji 

机构地区：[1]Department of Immunology, Basic Medical School Nanjing Medical University, Nanjing, Jiangsu 211166, China [2]Red Cross Blood Center, Nanjing, Jiangsu 210003, China [3]Rheumatology Department of Nanjing First Hospital Nanjing Medical University, Nanjing, Jiangsu, 210006, China

出　　处：《The Journal of Biomedical Research》2018年第2期113-122,共10页生物医学研究杂志（英文版）

摘　　要：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 P〈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-23 R and IL-17 A, 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.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 P〈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-23 R and IL-17 A, 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.

关 键 词：lupus erythematosus systemic（SLE） lymphotoxin β receptor（LTβR） interleukin-17（IL-17） interleukin-23 receptor（IL-23R） 

分 类 号：R593.241[医药卫生—内科学]