IL-17A production by renal ?? T cells promotes kidney injury in crescentic GN.

The Th17 immune response appears to contribute to the pathogenesis of human and experimental crescentic GN, but the cell types that produce IL-17A in the kidney, the mechanisms involved in its induction, and the IL-17A-mediated effector functions that promote renal tissue injury are incompletely understood. Here, using a murine model of crescentic GN, we found that CD4(+) T cells, ?? T cells, and a population of CD3(+)CD4(-)CD8(-)??T cell receptor(-)NK1.1(-) T cells all produce IL-17A in the kidney. A time course analysis identified ?? T cells as a major source of IL-17A in the early phase of disease, before the first CD4(+) Th17 cells arrived. The production of IL-17A by renal ?? T cells depended on IL-23p19 signaling and retinoic acid-related orphan receptor-?t but not on IL-1? or IL-6. In addition, depletion of dendritic cells, which produce IL-23 in the kidney, reduced IL-17A production by renal ?? T cells. Furthermore, the lack of IL-17A production in ?? T cells, as well as the absence of all ?? T cells, reduced neutrophil recruitment into the kidney and ameliorated renal injury. Taken together, these data suggest that ?? T cells produce IL-17A in the kidney, induced by IL-23, promoting neutrophil recruitment, and contributing to the immunopathogenesis of crescentic GN.     «

The Th17 immune response appears to contribute to the pathogenesis of human and experimental crescentic GN, but the cell types that produce IL-17A in the kidney, the mechanisms involved in its induction, and the IL-17A-mediated effector functions that promote renal tissue injury are incompletely understood. Here, using a murine model of crescentic GN, we found that CD4(+) T cells, ?? T cells, and a population of CD3(+)CD4(-)CD8(-)??T cell receptor(-)NK1.1(-) T cells all produce IL-17A in the kid...     »