Interleukin-17 activates human renal epithelial cells in vitro and is expressed during renal allograft rejection.

Local production of cytokines plays a critical role in the regulation of pathophysiologic processes leading to rejec- tion of transplanted organs. In the present study, the possible role of interleukin-l7 (lL-l7). a recently identified cytokine with tiniquc properties. was investigated. IL- I 7 is specifically produced by activated T cells, whereas biological activities arc restricted 10 the activalion of' nouhcnlatop(nctic cells. In 'itro, IL- I 7 inducediiiiary litiian proxinial tubular epithelial cells, a type of cell regulating local interstitial inflammatory re- spouses, to secrete higher levels of' IL-6, lL-8, and monocyte chenioultractant pn)tein- I , hut 1101 of the cheiuokine RANTES. The effect WLLS sl)ecific for IL- I 7, because it was coniplctely abrogated by a neutralii.ing anti-IL- I 7 antibody and WS dciii- onstrated to he tlose- IIIitI tilBe-del)efldeflt. In addition, IL- I 7 increased the production of complement component C3 by human proximal tubular epithebial cells, but not of other com- plement components. Immunofluorescence showed expression of IL- 17 in kidney biopsies from patients suffering from graft recction (8 of' 8 positive), whereas pretransplant biopsies and nornuil kidneys were negative (0 of' 6). Analysis of whole kidney isolates confirmed the presence of IL- I 7 mRNA by reverse transcription-PCR. IL- I 7 expression could also he lund in in '�'itr() cultured atid activated graft-infiltrating T cells. These results represent the first demonstration of IL- I 7 protein expression in pathologic conditions and suggest that IL- I 7 iiiight he ivuportant in the regulation of local inflaniiiia- tory responses.