{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:47:32Z","timestamp":1791323252095,"version":"4.3.1"},"reference-count":51,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cFondo di Ateneo per la Ricerca\u201d FAR 2019, University of Modena and Reggio Emilia","award":["E54I19002040005"],"award-info":[{"award-number":["E54I19002040005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Psoriasis is a chronic inflammatory skin disease characterized by dysregulation of the interleukin 17 (IL-17) signaling axis. Given that psoriasis development depends on keratinocyte stem cells and early progenitors\u2019 sensitivity to differentiation, we analyzed IL-17 ligands and the expression and function of in a novel subset of keratinocyte subpopulations: keratinocyte stem cells (KSC) and early and late Transit Amplifying (ETA or LTA, respectively) cells. We found that all subpopulations expressed all IL-17 variants, predominantly in ETA and LTA. Conversely, IL-17 receptor expression resulted in more heterogeneity, with IL-17RA, -C, and -E being the most differentially regulated. Stimulus with IL-17A, IL-17-F, IL-17-A\/F, and IL-17C promotes the upregulation of CXCL1, CXCL8, and DEFB4 mRNAs expression in both KSC and ETA. Moreover, IL-17A and IL-17A\/F mainly decrease KSC proliferation and promote cell cycle block. Globally, IL-17A and IL-17A\/F modulated the expression of proliferation, differentiation, and psoriasis-associated markers. Furthermore, KSC- and ETA-derived 3D reconstructions displayed increased epidermal thickness and upregulated KRT16 expression after treatment with IL-17A or IL-17A\/F. Therefore, our data demonstrated that IL-17 family members perform distinctive functions in a specific keratinocyte subpopulation and define IL-17 signaling as a critical modulator of KSC behavior, proving its role in epidermal homeostasis dysregulation of psoriasis.<\/jats:p>","DOI":"10.3390\/ijms26072989","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T12:18:52Z","timestamp":1742905132000},"page":"2989","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["IL-17 Ligand and Receptor Family Members Are Differentially Expressed by Keratinocyte Subpopulations and Modulate Their Differentiation and Inflammatory Phenotype"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0812-5524","authenticated-orcid":false,"given":"Elisabetta","family":"Palazzo","sequence":"first","affiliation":[{"name":"DermoLab, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2126-4147","authenticated-orcid":false,"given":"Roberta","family":"Lotti","sequence":"additional","affiliation":[{"name":"DermoLab, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7619-660X","authenticated-orcid":false,"given":"Marika","family":"Quadri","sequence":"additional","affiliation":[{"name":"DermoLab, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Pincelli","sequence":"additional","affiliation":[{"name":"DermoLab, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5667-5766","authenticated-orcid":false,"given":"Alessandra","family":"Marconi","sequence":"additional","affiliation":[{"name":"DermoLab, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/nri1689","article-title":"Getting under the skin: The immunogenetics of psoriasis","volume":"5","author":"Bowcock","year":"2005","journal-title":"Nat. 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