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<p>Sleep disturbances are a debilitating feature of psoriasis, but whether they arise from itching or from direct effects of inflammation on the brain remains unclear. Here we show, using clinical data and a mouse model of psoriasis-like inflammation, that affected animals exhibit marked wakefulness and fragmented non-rapid eye movement sleep, even when itching is eliminated. This sleep disruption is linked to overactivity of wake-promoting neurons in a brain region called the anterior hypothalamic area. We find evidence of a local inflammatory response in this region, including activation of microglia and elevated levels of the signaling protein tumor necrosis factor-alpha. Directly delivering an inhibitor of this protein into the anterior hypothalamic area significantly restores normal sleep. These findings reveal a direct pathway from skin inflammation to sleep-regulating brain circuits and identify tumor necrosis factor-alpha as a potential target for treating insomnia in psoriasis.</p><p></p>

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A dermo-hypothalamic axis driven by TNF-α mediates sleep disturbances in psoriasis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月17日

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  • Dandan Chen,
  • Ying Ma,
  • Jiliang Lu,
  • Xiaoya Xi,
  • Xinyi Dai,
  • Chenxingyue Zhang,
  • Ziyue Diao,
  • Xing Guo,
  • Zhiqiang Yin

摘要

Sleep disturbances are a debilitating feature of psoriasis, but whether they arise from itching or from direct effects of inflammation on the brain remains unclear. Here we show, using clinical data and a mouse model of psoriasis-like inflammation, that affected animals exhibit marked wakefulness and fragmented non-rapid eye movement sleep, even when itching is eliminated. This sleep disruption is linked to overactivity of wake-promoting neurons in a brain region called the anterior hypothalamic area. We find evidence of a local inflammatory response in this region, including activation of microglia and elevated levels of the signaling protein tumor necrosis factor-alpha. Directly delivering an inhibitor of this protein into the anterior hypothalamic area significantly restores normal sleep. These findings reveal a direct pathway from skin inflammation to sleep-regulating brain circuits and identify tumor necrosis factor-alpha as a potential target for treating insomnia in psoriasis.