{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T19:11:15Z","timestamp":1788894675652,"version":"build-2803163510"},"reference-count":72,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"IDI FARMACEUTICI SRL","award":["(Project entitled \u201cValutazione degli effetti anti-infiammatori e protettivi da danno ossidativo dei principi attivi L-cistina e nicotinammide in modelli pre-clinici di psoriasi\u201d e \u201cStudio della via delle chinurenine in pazienti affetti da psoriasi\u201d)"],"award-info":[{"award-number":["(Project entitled \u201cValutazione degli effetti anti-infiammatori e protettivi da danno ossidativo dei principi attivi L-cistina e nicotinammide in modelli pre-clinici di psoriasi\u201d e \u201cStudio della via delle chinurenine in pazienti affetti da psoriasi\u201d)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dysregulated cross-talk between immune cells and epithelial compartments is responsible for the onset and amplification of pathogenic auto-inflammatory circuits occurring in psoriasis. NAMPT-mediated NAD salvage pathway has been recently described as an immunometabolic route having inflammatory function in several disorders, including arthritis and inflammatory bowel diseases. To date, the role of NAD salvage pathway has not been explored in the skin of patients affected by psoriasis. Here, we show that NAD content is enhanced in lesional skin of psoriatic patients and is associated to high NAMPT transcriptional levels. The latter are drastically reduced in psoriatic skin following treatment with the anti-IL-17A biologics secukinumab. We provide evidence that NAMPT-mediated NAD+ metabolism fuels the immune responses executed by resident skin cells in psoriatic skin. In particular, intracellular NAMPT, strongly induced by Th1\/Th17-cytokines, acts on keratinocytes by inducing hyper-proliferation and impairing their terminal differentiation. Furthermore, NAMPT-mediated NAD+ boosting synergizes with psoriasis-related cytokines in the upregulation of inflammatory chemokines important for neutrophil and Th1\/Th17 cell recruitment. In addition, extracellular NAMPT, abundantly released by keratinocytes and dermal fibroblasts, acts in a paracrine manner on endothelial cells by inducing their proliferation and migration, as well as the expression of ICAM-1 membrane molecule and chemokines important for leukocyte recruitment into inflamed skin. In conclusion, our results showed that NAMPT-mediated NAD salvage pathway contributes to psoriasis pathogenic processes by amplifying epithelial auto-inflammatory responses in psoriasis.<\/jats:p>","DOI":"10.3390\/ijms22136860","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T11:07:40Z","timestamp":1624619260000},"page":"6860","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Enhanced NAMPT-Mediated NAD Salvage Pathway Contributes to Psoriasis Pathogenesis by Amplifying Epithelial Auto-Inflammatory Circuits"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0629-1729","authenticated-orcid":false,"given":"Laura","family":"Mercurio","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Immunology and Dermatology Division, IDI-IRCCS, I-00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7299-2393","authenticated-orcid":false,"given":"Martina","family":"Morelli","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology and Dermatology Division, IDI-IRCCS, I-00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Scarponi","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology and Dermatology Division, IDI-IRCCS, I-00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5622-7843","authenticated-orcid":false,"given":"Giovanni Luca","family":"Scaglione","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology and Dermatology Division, IDI-IRCCS, I-00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabatino","family":"Pallotta","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology and Dermatology Division, IDI-IRCCS, I-00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Avitabile","sequence":"additional","affiliation":[{"name":"IDI-Farmaceutici S.r.l. Pomezia, I-00171 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7537-6833","authenticated-orcid":false,"given":"Cristina","family":"Albanesi","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology and Dermatology Division, IDI-IRCCS, I-00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0585-6783","authenticated-orcid":false,"given":"Stefania","family":"Madonna","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology and Dermatology Division, IDI-IRCCS, I-00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.15252\/embj.201797135","article-title":"Modulating NAD + metabolism, from bench to bedside","volume":"36","author":"Katsyuba","year":"2017","journal-title":"EMBO J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.cmet.2018.02.011","article-title":"Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence","volume":"27","author":"Rajman","year":"2018","journal-title":"Cell Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1126\/science.aac4854","article-title":"NAD+ in aging, metabolism, and neurodegeneration","volume":"350","author":"Verdin","year":"2015","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.2174\/092986711795590101","article-title":"NAMPT in Regulated NAD Biosynthesis and its Pivotal Role in Human Metabolism","volume":"18","author":"Burgos","year":"2011","journal-title":"Curr. 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