Wüthrich R P, Sibalic V
Division of Nephrology, University Hospital, Zürich, Switzerland.
Exp Nephrol. 1998 Jul-Aug;6(4):288-93. doi: 10.1159/000020535.
Many forms of tubulointerstitial nephritis (TIN) may have an autoimmune origin. To understand the pathogenesis of autoimmune TIN it is important to examine suitable animal models where the initiation and development of tubulointerstitial diseases can be assessed with precision. Experimental models of autoimmune anti-tubular basement membrane (anti-TBM) disease for example have allowed to define the nephritogenic role of antibodies which target tubulointerstitial moieties. Several tubulointerstitial antigens which are recognized by specific anti-TBM antibodies have been characterized at a molecular level in these models. The CBA/CaH-kdkd mouse strain represents another model of TIN where complex T-cell networks are uniquely altered, resulting in cell-mediated interstitial nephritis. Characteristic tubular alterations (up-regulation of adhesion molecules and CD44, cytokine and chemokine secretion) are prominent in several models of experimental TIN, promoting T-cell and monocyte infiltration. The complex interplay between tubular epithelial cells and immune cells is probably a prerequisite for a coordinated immune response in many forms of TIN, resulting in autoimmune renal tubulointerstitial injury and ultimately in renal failure.
许多形式的肾小管间质性肾炎（TIN）可能有自身免疫起源。为了解自身免疫性TIN的发病机制，研究合适的动物模型很重要，在这些模型中可以精确评估肾小管间质性疾病的起始和发展。例如，自身免疫性抗肾小管基底膜（anti-TBM）疾病的实验模型已使人们能够确定靶向肾小管间质部分的抗体的致肾炎作用。在这些模型中，几种可被特异性抗TBM抗体识别的肾小管间质抗原已在分子水平上得到表征。CBA/CaH-kdkd小鼠品系代表了另一种TIN模型，其中复杂的T细胞网络发生独特改变，导致细胞介导的间质性肾炎。在几种实验性TIN模型中，特征性的肾小管改变（黏附分子和CD44上调、细胞因子和趋化因子分泌）很突出，促进T细胞和单核细胞浸润。肾小管上皮细胞与免疫细胞之间复杂的相互作用可能是多种形式的TIN中协调免疫反应的先决条件，导致自身免疫性肾小管间质损伤并最终导致肾衰竭。
