Collectively, the aforementioned work unveils a previously unidentified contribution of ANXA1 on preventing and relieving dermatitis-induced chronic itching and cholestatic itching through the inhibitory modulation of IL-17/IL-17R expression, astrocyte activation and TfR1-dependent iron overload in the spinal dorsal horn in mice, which has important implications for neuroinflammation control and itch management in clinical settings. Here, ANXA1 is linked to dermatitis.