The role of LIGHT in the pathogenesis of glomerulonephritis

LIGHT是TNF超家族的一员，据报道在T细胞活化和扩增过程中对共刺激分子起重要作用。先前的研究表明，用与LT和LIGHT结合的淋巴素(LT) β受体- ig融合蛋白（ltβ - ig）治疗啮齿动物，可防止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导致类似于人类IgA肾病（IgAN）的病理特征。这些数据提出了LIGHT参与肾小球肾炎发病机制的可能性，如IgAN或新月状肾小球肾炎。本研究的目的是通过实验性自身免疫性抗肾小球基底膜肾炎（EAG）或小鼠IgA肾病模型，探讨LIGHT在肾小球肾炎发病机制中的作用。为此，我们制备了ltbeta - ig，并验证ltbeta - ig处理是否可以预防IV型胶原的肾源性肽重组α 3(IV)NC1免疫WKY大鼠诱导的EAG。如前文所示，大鼠注射肾源性抗原后，肾小球80% - 100%出现重蛋白尿和新月形成，但本研究ltβ - ig治疗组与非治疗组之间无显著差异。

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.