The role of LIGHT in the pathogenesis of glomerulonephritis

LIGHT是肿瘤坏死因子超家族的成员之一，在T细胞活化和扩增过程中起着重要的共刺激分子作用。先前的研究已经表明，用与LT和LIGHT结合的光毒素（LT）β受体-Ig融合蛋白（LT β R-Ig）治疗啮齿动物，可以预防T细胞介导的自身免疫性疾病的发展。此外，失调的T细胞来源的LIGHT导致与人伊加肾病（IgAN）的病理特征相似的病理特征。这些数据提出了LIGHT参与肾小球肾炎（如IgAN或新月体肾小球肾炎）发病机制的可能性。本研究旨在通过实验性自身免疫性抗肾小球基底膜肾炎（EAG）和小鼠伊加肾病模型，探讨LIGHT在肾小球肾炎发病机制中的作用。为此，我们产生了LT β R-Ig，并验证了LT β R-Ig治疗是否能预防WKY大鼠中通过用致肾肽，IV型胶原蛋白的重组α 3（IV）NC 1免疫诱导的EAG。如前所述，注射致肾炎抗原的大鼠表现出严重的蛋白尿和80%至100%的肾小球中的新月体形成，但在我们的研究中，LT β R-Ig治疗组和非治疗组之间没有显著差异。

LIGHT, a member of TNF superfamily, has been reported to play a important role for costimulatory molecules in T cell activation and expansion. Previous studies have shown that treatment of rodents with a lymphotoxin (LT) beta receptor-Ig fusion protein (LTbetaR-Ig), which binds to both LT and LIGHT, prevents the development of Tcell-mediated autoimmune diseases. In addition, dysregulated T cell-derived LIGHT lead to pathological features similar to those of human IgA nephropathy (IgAN). These data raise the possibility that LIGHT is involved in the pathogenesis of glomerulonephritis, e.g, IgAN or crescentic glomerulonephritis. The aim of this study is to explore the involvement of LIGHT in the pathogenisis of glomerulonephritis by using experimental autoimmune anti-glomerular basement membranenephritis (EAG) or murin IgA nephropathy model. For this purpose, we generated LTbetaR-Ig and verified whether LTbetaR-Ig treatment prevents EAG induced in WKY rats by immunization with an nephritogenic peptide, recombinant alpha 3(IV)NC1 of type IV collagen. Rats injected with nephritogenic antigen showed heavy proteinuria and crescent formation in 80 to 100% of the glomeruli as shown previously, but there was no significant difference between LTbetaR-Ig-treament and non-treatment groups in our study.