Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands.
Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands.
Mol Immunol. 2015 Mar;64(1):82-9. doi: 10.1016/j.molimm.2014.11.003. Epub 2014 Nov 29.
Activation of the innate immunity through Toll-like receptors (TLRs) has been postulated to play an important role in the pathophysiology of renal allograft dysfunction. TLR2 and TLR4 dynamics in different human post-transplant pathological entities has never been studied. Therefore, we evaluated pre- and post-transplantation protein expression of TLR2 and TLR4 in human kidney biopsies. Human kidney biopsies obtained from living kidney donors and patients with acute tubular necrosis, acute cellular and vascular rejection and interstitial fibrosis/tubular atrophy (IF/TA) were used. Translating results from animal studies to the clinical situation is highly important considering the upcoming clinical studies with TLR inhibitors in human renal transplantation. Hence, the TLR2 and TLR4 expression in healthy mouse and rat kidneys was analyzed and compared with human kidneys. In healthy human kidneys, TLR2 is expressed on the endothelium and Bowman's capsule, while TLR4 is expressed on the endothelium only. No tubular staining was found for both receptors in human kidneys. In contrast to human biopsies, TLR2 and TLR4 expression in rodents was observed on tubular epithelial cells. In all acute rejection human biopsies, increased infiltration of TLR4(+) leukocytes was observed. In conclusion, a discrepancy exists between human and rodent renal TLR expression, which suggests careful attention when translating results from rodent studies to the human situation. Additionally, this study revealed human TLR2 and TLR4 expression dynamics in human biopsies pre- and post-transplantation.
通过 Toll 样受体 (TLR) 激活先天免疫被认为在肾移植功能障碍的病理生理学中发挥重要作用。TLR2 和 TLR4 在不同的人移植后病理实体中的动态变化从未被研究过。因此，我们评估了人类肾活检中 TLR2 和 TLR4 的移植前和移植后蛋白表达。使用来自活体供肾者和急性肾小管坏死、急性细胞和血管排斥以及间质纤维化/肾小管萎缩 (IF/TA) 患者的人类肾活检。考虑到即将进行的人类肾移植中 TLR 抑制剂的临床研究，将动物研究的结果转化为临床情况非常重要。因此，分析了健康小鼠和大鼠肾脏中 TLR2 和 TLR4 的表达，并与人类肾脏进行了比较。在健康的人类肾脏中，TLR2 表达在内皮细胞和 Bowman 囊上，而 TLR4 仅表达在内皮细胞上。在人类肾脏中，两种受体均未在肾小管上发现染色。与人类活检相比，在啮齿动物中观察到 TLR2 和 TLR4 表达在肾小管上皮细胞上。在所有急性排斥的人类活检中，观察到 TLR4(+)白细胞浸润增加。总之，人类和啮齿动物肾脏 TLR 表达之间存在差异，这表明在将啮齿动物研究结果转化为人类情况时需要谨慎。此外，本研究揭示了人类 TLR2 和 TLR4 在移植前和移植后人类活检中的表达动态。
