EFFECTOR AND REGULATORY INTERSTITIAL INFLAMMATORY CELLS IN CHRONIC PROTEINURIC RENAL DISEASE

目前对慢性肾病的治疗是无效的。结果，肾衰竭发展到病人需要透析或移植来维持生命的阶段。每年有近1600名澳大利亚人因此开始透析，更多的人死于肾衰竭或其并发症。这个项目将使我们更好地了解肾衰竭进展的原因，并将确定更有效的治疗方法来预防进展。在所有类型的进行性慢性肾脏疾病中，肾脏内的支持组织（间质）被炎症细胞浸润。间质炎症的数量对肾衰竭的严重程度和肾脏疾病进展到终末期的速度有重要影响。这些炎症细胞浸润间质的原因，以及它们在肾脏疾病进展中的确切作用，目前还不完全清楚。例如，这些炎症细胞中的一些似乎会导致肾脏瘢痕形成，而另一些似乎具有保护作用。此外，尽管它们是减缓肾脏疾病进展的明显治疗靶点，但目前的治疗在很大程度上是无效的，因为它们不能区分不同类型的炎症细胞，以及这些细胞是造成还是防止损害。我们的实验室最近开发了一个强大的慢性肾脏疾病模型，该模型将用于检查不同类型间质炎症细胞对肾脏疾病进展的影响。到目前为止，我们已经证明，一种类型的炎症细胞（CD4淋巴细胞）的消耗使疾病进程恶化，而另外两种类型的细胞（CD8淋巴细胞或巨噬细胞）的消耗具有保护作用。这提出了一种真实而令人兴奋的可能性，即针对特定炎症细胞的治疗可能在治疗人类进行性肾脏疾病中有效。

Current treatments for chronic kidney disease are ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year almost 1600 Australians commence dialysis for this reason, and many more die of kidney failure or its complications. This project will lead to a greater understanding of why kidney failure progresses, and will define more effective treatments for preventing progression. In progressive chronic kidney diseases of all types, the supporting tissue within the kidney (the interstitium) becomes infiltrated with inflammatory cells. The amount of interstitial inflammation has an important bearing on the severity of kidney failure, and the rate at which kidney disease progresses to endstage. The reasons that these inflammatory cells infiltrate the interstitium, and their exact role in the progression of kidney disease are only partially understood. For example, some of these inflammatory cells appear to cause kidney scarring, whereas others appear to be protective. Moreover, even though they are obvious targets for treatment aimed at slowing the progression of kidney disease, current treatments are largely ineffective as they do not differentiate between the different types of inflammatory cells, and whether these cells are causing or preventing damage. Our laboratory has recently developed a robust model of chronic kidney disease, which will be used to examine the effect of individual types of interstitial inflammatory cells on the progression of kidney disease. So far we have shown that depletion of one type of inflammatory cell (CD4 lymphocytes) worsened the disease process, whereas depletion of two other cell types (CD8 lymphocytes or macrophages) was protective. This raises the real and exciting possibility that treatment directed against specific inflammatory cells may be effective in the treatment of progressive kidney disease in humans.