The ultraviolet B radiation (UVB) causes skin inflammation, which contributes to the causality and the exacerbation of a number of cutaneous diseases. However, the mechanism of UVB-driven inflammation in the skin remains poorly understood. We show that ferroptosis, a non-apoptotic programmed cell death pathway that is promoted by an excessive phospholipid peroxidation, is activated in the epidermal keratinocytes after their exposure to UVB. The susceptibility of the keratinocytes to UVB-induced ferroptosis depends on the extent of pro-ferroptosis death signal generation and the dysregulation of the glutathione system. Inhibition of ferroptosis prevents the release of HMGB1 from the human epidermal keratinocytes, and blocks necroinflammation in the UVB-irradiated mouse skin. We show that while apoptosis and pyroptosis are also detectable in the keratinocytes after UVB exposure, ferroptosis plays a significant role in initiating UVB-induced inflammation in the skin. Our results have important implications for the prevention and the treatment of a broad range of skin diseases which are fostered by UVB-induced inflammation.

紫外线 B 辐射 (UVB) 会导致皮肤发炎，从而导致许多皮肤疾病的因果关系和恶化。然而，UVB 驱动的皮肤炎症的机制仍然知之甚少。我们表明，铁死亡是一种由过度磷脂过氧化促进的非凋亡程序性细胞死亡途径，在暴露于 UVB 后在表皮角质形成细胞中被激活。角质形成细胞对 UVB 诱导的铁死亡的敏感性取决于促铁死亡信号产生的程度和谷胱甘肽系统的失调。抑制铁死亡可防止 HMGB1 从人表皮角质形成细胞中释放，并阻止 UVB 照射的小鼠皮肤中的坏死性炎症。我们表明，虽然在 UVB 暴露后角质形成细胞中也可检测到细胞凋亡和细胞焦亡，但铁死亡在引发 UVB 诱导的皮肤炎症中起重要作用。我们的研究结果对预防和治疗由 UVB 引起的炎症引起的多种皮肤病具有重要意义。