IL-17 expression as a possible predictive parameter for subclinical renal allograft rejection

Abstract

In the present study we have tried to establish the role of IL-17 in subclinical renal allograft rejection. In this animal model, renal grafts from BN (RT1") were transplanted heterotopically into LEW (RT1') rats. As controls, LEW grafts were transplanted into LEW rats. The histopathological examination demonstrated that the changes in the allograft kidney on day 2 were similar to those ranked as borderline changes according to the Banff classification scale. On day 2, the serum level of blood urea nitrogen (BUN) and creatinine were the same as on day 1. The examination of allograft cytokines mRNA showed that IL-17 mRNA expressed earlier on the second postoperative day, peaked at day 5, and then declined, becoming almost undetectable at day 9, when most rats died. IL-17 antigen was also proven, by histochemical staining, to be expressed early, however we could not find the same early appearance on other Thl/Th2 cytokines. In human renal biopsy samples, the IL-17 antigen could be found scattered around in the borderline changed rejected renal allografts without evidence of a serum creatinine increase, but was undetectable both in normal controls and in renal transplant tissue without signs of rejection. IL-17 mRNA was detected in the mononuclear cells of the urinary sediment of patients suffering from borderline subclinical rejection. From the above results we can hypothesize that IL-17 could serve as a predictive parameter for borderline subclinical renal allograft rejection in the future.

Review: The function of regulatory T cells at the ocular surface

“…Furthermore, treatment with monoclonal anti-IL-17A was shown to result in rejection of 90% of corneal allografts. These findings are consistent with other transplantation immunology reports of IL-17 playing an important role in the tolerance of cardiac and renal allografts [112,113]. …”

“…Indeed, in cases there the local microenvironment remains inflamed, Tregs may be prone to change phenotype. Th17 cells have been proposed as mediating an alternative pathway of allograft rejection [124], with IL-17 implicated in transplant rejection [112,113]. Indeed, IL-17 antagonism has been demonstrated to delay graft rejection in murine models of transplantation [125,126].…”

Increased expression of interleukin 17 in inflammatory bowel disease

“…[19][20][21][22] IL-17 has been implicated in several inflammatory disorders, such as rheumatoid arthritis, multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, psoriasis, Helicobacter pylori associated gastritis, bronchial asthma, and renal allograft rejection. [21][22][23][24][25][26][27][28][29] However, the pathophysiological role of IL-17 in IBD remains unclear. In this study we investigated IL-17 expression in IBD patients.…”

Differential regulation of interleukin 17 and interferon production in inflammatory bowel disease

“…Both subsets can originate from a CD161 + CD4 + natural killer (NK) T cell precursors present in the umbilical cord blood, in the presence of IL1β and IL23 as polarising cytokines, but whether this pathway is important in vivo in man is not known 8. Many chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes,9 and IL17 over-expression has been found in a number of inflammatory disorders, including IBD 10 11 12 13 14 15 16 17. However, the relative roles of Th1/Th17 cells in chronic gut inflammation is still under debate.…”