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Under periodontitis, sleep restriction increased the secretion of substance P from trigeminal neurons in the periodontium, enhancing vasodilation and vascular permeability, which in turn promoted the infiltration of proinflammatory immune cells. Blocking substance P signaling via a Neurokinin-1 receptor antagonist or knocking down Tacr1 in vascular endothelial cells alleviated these detrimental effects. Our findings unveil a critical neuron-vessel-immune axis that exacerbates periodontitis during sleep deficiency and suggest potential therapeutic strategies targeting this axis for managing periodontitis in individuals suffering from sleep deficiency.<\/jats:p>","DOI":"10.1073\/pnas.2424169122","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T15:00:42Z","timestamp":1749481242000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":13,"title":["Sleep deficiency exacerbates periodontal inflammation via trigeminal TRPV1 neurons"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5794-0809","authenticated-orcid":false,"given":"Junhui","family":"Li","sequence":"first","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration and Tongji Research Institute of Stomatology and Department of Implantology, Shanghai Tongji 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