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Renal expression of Toll-like receptor 2 and 4: Dynamics in human allograft injury and comparison to rodents

Stribos, Elisabeth G.D., van Werkhoven, Maaike B., Poppelaars, Felix, van Goor, Harry, Olinga, Peter, van Son, Willem J., Damman, Jeffrey, Seelen, Marc A.
Molecular Immunology 2015 v.64 pp. 82-89
Toll-like receptor 2, Toll-like receptor 4, allografting, atrophy, biopsy, clinical trials, endothelium, epithelial cells, fibrosis, humans, innate immunity, kidney transplant, kidneys, leukocytes, mice, necrosis, pathophysiology, patients, protein synthesis, rats, staining
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.