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NAD\n                    <jats:sup>+<\/jats:sup>\n                    is synthesized from nicotinamide, nicotinic acid (collectively termed niacin), and tryptophan. In humans, deficiencies in these nutrients result in pellagra, marked by dermatitis, diarrhea, and dementia. The dermatitis associated with pellagra typically manifests as photodermatosis in sun-exposed areas. This study examined the effects of NAD\n                    <jats:sup>+<\/jats:sup>\n                    deficiency on skin homeostasis using epidermis-specific Nampt\u2013conditional KO (Nampt-cKO) mice. These mice displayed substantial NAD\n                    <jats:sup>+<\/jats:sup>\n                    depletion, reduced poly(ADP-ribose) polymerase (PARP) activity, and increased DNA damage. Consequently, Nampt-cKO mice developed spontaneous skin inflammation and epidermal hyperplasia. RNA-seq and IHC analyses demonstrated increased IL-36 cytokine expression, suggesting that DNA repair\u2013related genomic stress triggers keratinocyte-driven IL-36 production, which promotes inflammation. Furthermore, reduced COL17A1 expression and elevated thymic stromal lymphopoietin (TSLP) levels were observed. NAD\n                    <jats:sup>+<\/jats:sup>\n                    repletion by transdermal supplementation of nicotinamide mononucleotide (NMN) suppressed the rise of IL-36 levels and skin inflammation. These findings underscore the importance of Nampt-mediated NAD\n                    <jats:sup>+<\/jats:sup>\n                    metabolism for epidermal stability and indicate that NAD\n                    <jats:sup>+<\/jats:sup>\n                    depletion may contribute to IL-36\u2013mediated skin inflammation, offering insights for therapeutic strategies in inflammatory skin disorders.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.189177","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T17:00:37Z","timestamp":1770742837000},"source":"Crossref","is-referenced-by-count":1,"title":["Epidermal NAD+ deficiency induces IL-36\u2013mediated skin inflammation and acanthosis"],"prefix":"10.1172","volume":"11","author":[{"given":"Taiki","family":"Seki","sequence":"first","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, Faculty of Medicine,"},{"name":"Department of Dermatology, Faculty of Medicine, 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