CD103⁺ dendritic cells (DCs) in nonlymphoid organs exhibit two main functions: maintaining tolerance by induction of regulatory T cells and protecting against tissue infection through cross-presentation of foreign antigens to CD8⁺ T cells. However, the role of CD103⁺ DCs in kidney disease is unknown. In this study, we show that CD103⁺ DCs are one of four subpopulations of renal mononuclear phagocytes in normal kidneys. CD103⁺ DCs expressed DC-specific surface markers, transcription factors, and growth factor receptors and were found in the kidney cortex but not in the medulla. The number of kidney CD103⁺ DCs was significantly higher in mice with adriamycin nephropathy (AN) than in normal mice, and depletion of CD103⁺ DCs attenuated kidney injury in AN mice. In vitro, kidney CD103⁺ DCs preferentially primed CD8⁺ T cells and did not directly induce tubular epithelial cell apoptosis. Adoptive transfer of CD8⁺ T cells significantly exacerbated kidney injury in AN SCID mice, whereas depletion of CD103⁺ DCs in these mice impaired activation and proliferation of transfused CD8⁺ T cells and prevented the exacerbation of kidney injury associated with this transfusion. In conclusion, kidney CD103⁺ DCs display a pathogenic role in murine CKD via activation of CD8⁺ T cells.