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Immunol."],"abstract":"<jats:p>Abnormal skin pigmentation is a common clinical dermatological issue, and its occurrence and development are closely associated with the inflammatory microenvironment. However, the interactive regulatory mechanisms between inflammatory factors and melanogenesis remain incompletely understood. In this study, through the analysis of transcriptomic data from melasma, psoriasis, acne, atopic dermatitis, and ultraviolet-irradiated skin tissues, we found that CXCL1 may negatively regulate melanogenesis. To validate this finding, we exogenously treated human primary melanocytes, MNT1 cells, and ex vivo human foreskin tissues with CXCL1. The results showed that CXCL1 reduced melanin content, tyrosinase activity, and the expression of key melanogenesis-related genes, including MITF, TYR, TYRP1, and DCT. Mechanistic studies revealed that CXCL1 exerts these inhibitory effects through its canonical receptor CXCR2. Notably, CXCL1 treatment significantly decreased both the expression level and nuclear translocation of \u03b2-catenin, a key effector molecule of the WNT signaling pathway, and this effect was effectively reversed by the specific CXCR2 inhibitor SB225002, suggesting that the CXCL1-CXCR2 axis negatively regulates melanogenesis by suppressing the WNT\/\u03b2-catenin signaling pathway. In summary, this study elucidates a preliminary mechanism by which the CXCL1-CXCR2 axis negatively regulates melanogenesis through inhibition of the WNT\/\u03b2-catenin signaling pathway, linking inflammatory cytokine networks to the regulatory machinery of melanogenesis. It provides novel perspectives for deciphering the pathogenesis of pigmentary skin disorders and developing therapeutic strategies with combined anti-inflammatory and depigmenting effects.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1907373","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:25:23Z","timestamp":1785471923000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CXCL1-CXCR2 axis inhibits melanogenesis through the suppression of the WNT\/\u03b2-catenin pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Yushan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Dermatology, The Third Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Third Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Changde Hospital, Xiangya School of Medicine, Central South University, The First People\u2019s Hospital of Changde City","place":["Changde, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojiao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Changde Hospital, Xiangya School of Medicine, Central South University, The First People\u2019s Hospital of Changde City","place":["Changde, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Third Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Changde Hospital, Xiangya School of Medicine, Central South University, The First People\u2019s Hospital of Changde City","place":["Changde, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyang","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Third Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1159\/000518826","article-title":"Influence of ethnicities and skin color variations in different populations: a review","volume":"35","author":"Naik","year":"2022","journal-title":"Skin Pharmacol Physiol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2024.08.023","article-title":"Photoprotective melanin is maintained within keratinocytes in storage lysosomes","volume":"145","author":"Neto","year":"2025","journal-title":"J Invest Dermatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2022.09.525","article-title":"NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism","volume":"184","author":"Allouche","year":"2021","journal-title":"Cell"},{"key":"B4","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.addr.2020.02.002","article-title":"Topical treatment strategies to manipulate human skin pigmentation","volume":"153","author":"Rachmin","year":"2020","journal-title":"Adv Drug Delivery Rev"},{"key":"B5","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.jaad.2021.12.065","article-title":"Disorders of hyperpigmentation. 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