{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:13:10Z","timestamp":1792681990702,"version":"4.5.0"},"reference-count":107,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005743","name":"Universit\u00e0 Cattolica del Sacro Cuore","doi-asserted-by":"publisher","award":["Linea D1"],"award-info":[{"award-number":["Linea D1"]}],"id":[{"id":"10.13039\/501100005743","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Skin is the forestage for a series of many-sided functions of tumor necrosis factor-alpha (TNF-\u03b1), a proinflammatory cytokine with staggering versatility and sizable implications for tissue homeostasis, immune responses, angiogenesis, apoptosis, local and systemic inflammation. An aberrant TNF-\u03b1-mediated crosstalk has been linked to the pathogenesis of acute and chronic skin inflammatory diseases, and indeed, TNF-\u03b1 dysregulation can contribute to the development and progression of psoriasis, vitiligo, local damage following exposition to ultraviolet light radiations, cutaneous lupus erythematosus, and acne vulgaris. Therapies that target TNF-\u03b1 are conspicuously used in the treatment of different skin disorders, aiming to modulate the in vivo immune functions triggered by many cutaneous cells, including keratinocytes, mast cells, or Langerhans cells, and reduce inflammation taking place within the skin. Herein, we focus on the key relationships between TNF-\u03b1 and distinct skin non-neoplastic inflammatory or physiologic conditions, showing that a natural induction of TNF-\u03b1 may have a protective significance but that TNF-\u03b1 overproduction may be harmful or even lethal. Many questions remain unraveled in the therapeutic practice, and caution should be exercised due to eventual backlashes exerted by TNF-\u03b1 in maintaining skin health or in provoking skin disease.<\/jats:p>","DOI":"10.3390\/ijms25147762","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T09:46:57Z","timestamp":1721123217000},"page":"7762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Tumor Necrosis Factor-Alpha: Ally and Enemy in Protean Cutaneous Sceneries"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2456-5308","authenticated-orcid":false,"given":"Krizia","family":"Pocino","sequence":"first","affiliation":[{"name":"Unit\u00e0 Operativa Complessa di Patologia Clinica, Ospedale San Pietro Fatebenefratelli, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Carnazzo","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Santa Maria Goretti Hospital, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9730-5836","authenticated-orcid":false,"given":"Annunziata","family":"Stefanile","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Complessa di Patologia Clinica, Ospedale San Pietro Fatebenefratelli, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9716-070X","authenticated-orcid":false,"given":"Valerio","family":"Basile","sequence":"additional","affiliation":[{"name":"Clinical Pathology Unit and Cancer Biobank, Department of Research and Advanced Technologies, Regina Elena National Cancer Institute IRCCS, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Guerriero","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9155-6378","authenticated-orcid":false,"given":"Mariapaola","family":"Marino","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia Traslazionale, Universit\u00e0 Cattolica Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7032-7779","authenticated-orcid":false,"given":"Donato","family":"Rigante","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Life Sciences and Public Health, Universit\u00e0 Cattolica Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8328-2570","authenticated-orcid":false,"given":"Umberto","family":"Basile","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Santa Maria Goretti Hospital, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1182\/blood-2011-04-325225","article-title":"Historical Perspectives on Tumor Necrosis Factor and Its Superfamily: 25 Years Later, a Golden Journey","volume":"119","author":"Aggarwal","year":"2012","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Li, L., Lu, J., Liu, J., Wu, J., Zhang, X., Meng, Y., Wu, X., Tai, Z., Zhu, Q., and Chen, Z. 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