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A grain of salt on kidney dendritic cell function in allograft rejection. Acute kidney graft allorejection affects primarily the renal cortex. The present study by Chessa et al. offers an explanation for this phenomenon. The authors employ microarray-based gene expression analysis to provide evidence that the hyperosmolarity of the renal medulla induces a transcriptional fingerprint associated with anti-inflammatory functionality in medullary dendritic cells, which may attenuate local alloreactivity. This novel immunoregulatory mechanism hints at a new opportunity to prevent allorejection.