{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:46:15Z","timestamp":1768506375175,"version":"3.49.0"},"posted":{"date-parts":[[2023,5,22]]},"group-title":"Cell Biology","reference-count":82,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Vitiligo is an autoimmune skin disease caused by cutaneous melanocyte loss. Although phototherapy and T cell suppression therapy have been widely used to induce epidermal re-pigmentation, full pigmentation recovery is rarely achieved due to our poor understanding of the cellular and molecular mechanisms governing this process. Here, we identify unique melanocyte stem cell (McSC) epidermal migration rates between male and female mice, which is due to sexually dimorphic cutaneous inflammatory responses generated by ultra-violet B exposure. Using genetically engineered mouse models, and unbiased bulk and single-cell mRNA sequencing approaches, we determine that manipulating the inflammatory response through cyclooxygenase and its downstream prostaglandin product regulates McSC proliferation and epidermal migration in response to UVB exposure. Furthermore, we demonstrate that a combinational therapy that manipulates both macrophages and T cells (or innate and adaptive immunity) significantly promotes epidermal melanocyte re-population. With these findings, we propose a novel therapeutic strategy for repigmentation in patients with depigmentation conditions such as vitiligo.<\/jats:p>","DOI":"10.1101\/2023.05.22.541644","type":"posted-content","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T02:35:11Z","timestamp":1684809311000},"source":"Crossref","is-referenced-by-count":0,"title":["Sexual dimorphism in melanocyte stem cell behavior reveals combinational therapeutic strategies for cutaneous repigmentation"],"prefix":"10.64898","author":[{"given":"Luye","family":"An","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dahihm","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leanne","family":"Donahue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menansili Abraham","family":"Mejooli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi-Yong","family":"Eom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nozomi","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5436-5377","authenticated-orcid":false,"given":"Andrew C","family":"White","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023052412500721000_2023.05.22.541644v1.1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1159\/000506103","article-title":"Vitiligo: A Review","volume":"236","year":"2020","journal-title":"Dermatology (Basel)"},{"key":"2023052412500721000_2023.05.22.541644v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2016.10.048"},{"key":"2023052412500721000_2023.05.22.541644v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60763-7"},{"key":"2023052412500721000_2023.05.22.541644v1.4","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-021-00631-6"},{"key":"2023052412500721000_2023.05.22.541644v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.det.2016.11.014"},{"key":"2023052412500721000_2023.05.22.541644v1.6","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1001\/jamadermatol.2015.1520","article-title":"Tofacitinib Citrate for the Treatment of Vitiligo: A Pathogenesis-Directed Therapy","volume":"151","year":"2015","journal-title":"JAMA Dermatol"},{"key":"2023052412500721000_2023.05.22.541644v1.7","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jaad.2015.09.073","article-title":"Rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitiligo and alopecia areata (AA)","volume":"74","year":"2016","journal-title":"J. Am. Acad. Dermatol"},{"key":"2023052412500721000_2023.05.22.541644v1.8","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/S0140-6736(20)30609-7","article-title":"Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial","volume":"396","year":"2020","journal-title":"Lancet"},{"key":"2023052412500721000_2023.05.22.541644v1.9","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1056\/NEJMoa2118828","article-title":"Two phase 3, randomized, controlled trials of ruxolitinib cream for vitiligo","volume":"387","year":"2022","journal-title":"N. Engl. J. Med"},{"key":"2023052412500721000_2023.05.22.541644v1.10","doi-asserted-by":"publisher","DOI":"10.4103\/0019-5154.57604"},{"key":"2023052412500721000_2023.05.22.541644v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2006.07.008"},{"key":"2023052412500721000_2023.05.22.541644v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.44"},{"key":"2023052412500721000_2023.05.22.541644v1.13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006636"},{"key":"2023052412500721000_2023.05.22.541644v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3194"},{"key":"2023052412500721000_2023.05.22.541644v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.235"},{"key":"2023052412500721000_2023.05.22.541644v1.16","doi-asserted-by":"publisher","DOI":"10.1101\/gad.340281.120"},{"key":"2023052412500721000_2023.05.22.541644v1.17","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1038\/jid.2013.9","article-title":"UVB-induced melanocyte proliferation in neonatal mice driven by CCR2-independent recruitment of Ly6c(low)MHCII(hi) macrophages","volume":"133","year":"2013","journal-title":"J. Invest. Dermatol"},{"key":"2023052412500721000_2023.05.22.541644v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/nature09666"},{"key":"2023052412500721000_2023.05.22.541644v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-1935-3"},{"key":"2023052412500721000_2023.05.22.541644v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.09.001"},{"key":"2023052412500721000_2023.05.22.541644v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.463"},{"key":"2023052412500721000_2023.05.22.541644v1.22","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.1002\/cpim.63","article-title":"Mouse model for human vitiligo","volume":"124","year":"2019","journal-title":"Curr. Protoc. Immunol"},{"key":"2023052412500721000_2023.05.22.541644v1.23","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13619-022-00132-9","article-title":"A mouse model of vitiligo based on endogenous auto-reactive CD8 + T cell targeting skin melanocyte","volume":"11","year":"2022","journal-title":"Cell Regen (Lond"},{"key":"2023052412500721000_2023.05.22.541644v1.24","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092436"},{"key":"2023052412500721000_2023.05.22.541644v1.25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2011.00832.x"},{"key":"2023052412500721000_2023.05.22.541644v1.26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms140612222"},{"key":"2023052412500721000_2023.05.22.541644v1.27","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1039\/c5pp00098j","article-title":"Hair follicle melanocyte precursors are awoken by ultraviolet radiation via a cell extrinsic mechanism","volume":"14","year":"2015","journal-title":"Photochem Photobiol Sci"},{"key":"2023052412500721000_2023.05.22.541644v1.28","doi-asserted-by":"publisher","DOI":"10.1126\/science.1184733"},{"key":"2023052412500721000_2023.05.22.541644v1.29","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20205"},{"key":"2023052412500721000_2023.05.22.541644v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2467"},{"key":"2023052412500721000_2023.05.22.541644v1.31","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1111\/jdv.15348","article-title":"Gender differences, UV exposure and risk of lentigo maligna in a nationwide healthcare population cohort study","volume":"33","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol"},{"key":"2023052412500721000_2023.05.22.541644v1.32","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1007\/s40471-019-00192-7","article-title":"Sex differences in melanoma","volume":"6","year":"2019","journal-title":"Curr. Epidemiol. Rep"},{"key":"2023052412500721000_2023.05.22.541644v1.33","unstructured":"Incidence of Malignant Melanoma of the Skin\u2013United States, 2009\u20132018 | CDC. At <https:\/\/www.cdc.gov\/cancer\/uscs\/about\/data-briefs\/no28-melanoma-2018.htm>"},{"key":"2023052412500721000_2023.05.22.541644v1.34","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1988.tb01746.x"},{"key":"2023052412500721000_2023.05.22.541644v1.35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2007.03332.x"},{"key":"2023052412500721000_2023.05.22.541644v1.36","doi-asserted-by":"publisher","DOI":"10.2302\/kjm.54.165"},{"key":"2023052412500721000_2023.05.22.541644v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2007.02.010"},{"key":"2023052412500721000_2023.05.22.541644v1.38","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.3389\/fimmu.2019.01059","article-title":"Mechanisms of Inflammation in Neutrophil-Mediated Skin Diseases","volume":"10","year":"2019","journal-title":"Front. Immunol"},{"key":"2023052412500721000_2023.05.22.541644v1.39","first-page":"20","article-title":"Postinflammatory hyperpigmentation: a review of the epidemiology, clinical features, and treatment options in skin of color","volume":"3","year":"2010","journal-title":"J. Clin. Aesthet. Dermatol"},{"key":"2023052412500721000_2023.05.22.541644v1.40","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.2011.04088.x"},{"key":"2023052412500721000_2023.05.22.541644v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/nature24271"},{"key":"2023052412500721000_2023.05.22.541644v1.42","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0802999"},{"key":"2023052412500721000_2023.05.22.541644v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.015"},{"key":"2023052412500721000_2023.05.22.541644v1.44","doi-asserted-by":"crossref","first-page":"eabl7482","DOI":"10.1126\/sciimmunol.abl7482","article-title":"A common framework of monocyte-derived macrophage activation","volume":"7","year":"2022","journal-title":"Sci. Immunol."},{"key":"2023052412500721000_2023.05.22.541644v1.45","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2859"},{"key":"2023052412500721000_2023.05.22.541644v1.46","doi-asserted-by":"crossref","unstructured":"Atri, C. , Guerfali, F. Z. & Laouini, D . Role of Human Macrophage Polarization in Inflammation during Infectious Diseases. Int. J. Mol. Sci. 19, (2018).","DOI":"10.3390\/ijms19061801"},{"key":"2023052412500721000_2023.05.22.541644v1.47","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.7.3985"},{"key":"2023052412500721000_2023.05.22.541644v1.48","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/19.5.723"},{"key":"2023052412500721000_2023.05.22.541644v1.49","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2003.12495.x"},{"key":"2023052412500721000_2023.05.22.541644v1.50","doi-asserted-by":"publisher","DOI":"10.1038\/nature05541"},{"key":"2023052412500721000_2023.05.22.541644v1.51","doi-asserted-by":"publisher","DOI":"10.1002\/gene.20192"},{"key":"2023052412500721000_2023.05.22.541644v1.52","doi-asserted-by":"publisher","DOI":"10.1038\/nature10573"},{"key":"2023052412500721000_2023.05.22.541644v1.53","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.69.1.145"},{"key":"2023052412500721000_2023.05.22.541644v1.54","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gni051"},{"key":"2023052412500721000_2023.05.22.541644v1.55","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.236927"},{"key":"2023052412500721000_2023.05.22.541644v1.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.08.015"},{"key":"2023052412500721000_2023.05.22.541644v1.57","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s12935-015-0260-7","article-title":"Cyclooxygenase-2 promotes tumor growth and suppresses tumor immunity","volume":"15","year":"2015","journal-title":"Cancer Cell Int"},{"key":"2023052412500721000_2023.05.22.541644v1.58","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1612920114"},{"key":"2023052412500721000_2023.05.22.541644v1.59","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1093\/oxfordjournals.jbchem.a132272","article-title":"Studies on 15-hydroxyprostaglandin dehydrogenase with various prostaglandin analogues","volume":"84","year":"1978","journal-title":"J. Biochem"},{"key":"2023052412500721000_2023.05.22.541644v1.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.02.003"},{"key":"2023052412500721000_2023.05.22.541644v1.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.015"},{"key":"2023052412500721000_2023.05.22.541644v1.62","unstructured":"FDA approves topical treatment addressing repigmentation in vitiligo in patients aged 12 and older | FDA. At <https:\/\/www.fda.gov\/drugs\/news-events-human-drugs\/fda-approves-topical-treatment-addressing-repigmentation-vitiligo-patients-aged-12-and-older>"},{"key":"2023052412500721000_2023.05.22.541644v1.63","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1016\/j.jid.2022.05.1093","article-title":"Addition of Narrow-Band UVB Phototherapy to Ruxolitinib Cream in Patients With Vitiligo","volume":"142","year":"2022","journal-title":"J. Invest. Dermatol"},{"key":"2023052412500721000_2023.05.22.541644v1.64","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0002-9378(89)80020-1","article-title":"Prostaglandin E2 gel for cervical ripening and induction of labor: a critical analysis","volume":"160","year":"1989","journal-title":"Am. J. Obstet. Gynecol"},{"key":"2023052412500721000_2023.05.22.541644v1.65","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1046\/j.1365-4362.2002.01612.x","article-title":"Topical prostaglandin analog (PGE2) in vitiligo--a preliminary study","volume":"41","year":"2002","journal-title":"Int. J. Dermatol"},{"key":"2023052412500721000_2023.05.22.541644v1.66","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1111\/j.1365-2133.2008.08923.x","article-title":"Evaluation of safety and efficacy of topical prostaglandin E2 in treatment of vitiligo","volume":"160","year":"2009","journal-title":"Br. J. Dermatol"},{"key":"2023052412500721000_2023.05.22.541644v1.67","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/s41586-022-04833-8","article-title":"Androgen receptor blockade promotes response to BRAF\/MEK-targeted therapy","volume":"606","year":"2022","journal-title":"Nature"},{"key":"2023052412500721000_2023.05.22.541644v1.68","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1038\/s41467-022-30398-1","article-title":"Raising the bar on sex and gender reporting in research","volume":"13","year":"2022","journal-title":"Nat. Commun."},{"key":"2023052412500721000_2023.05.22.541644v1.69","doi-asserted-by":"crossref","first-page":"103512","DOI":"10.1016\/j.etap.2020.103512","article-title":"Gender differences in UV-induced skin inflammation, skin carcinogenesis and systemic damage","volume":"81","year":"2021","journal-title":"Environ Toxicol Pharmacol"},{"key":"2023052412500721000_2023.05.22.541644v1.70","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgs223"},{"key":"2023052412500721000_2023.05.22.541644v1.71","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199958020-00017"},{"key":"2023052412500721000_2023.05.22.541644v1.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2004.10.861"},{"key":"2023052412500721000_2023.05.22.541644v1.73","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-14-329"},{"key":"2023052412500721000_2023.05.22.541644v1.74","first-page":"74","article-title":"Possible mechanisms in the induction of vitiligo-like hypopigmentation by topical imiquimod","volume":"33","year":"2008","journal-title":"Clin. Exp. Dermatol"},{"key":"2023052412500721000_2023.05.22.541644v1.75","doi-asserted-by":"crossref","first-page":"1049079","DOI":"10.3389\/fimmu.2022.1049079","article-title":"Neutrophils inhibit \u03b3\u03b4 T cell functions in the imiquimod-induced mouse model of psoriasis","volume":"13","year":"2022","journal-title":"Front. Immunol"},{"key":"2023052412500721000_2023.05.22.541644v1.76","doi-asserted-by":"crossref","first-page":"637504","DOI":"10.3389\/fonc.2021.637504","article-title":"Cyclooxygenase-2 Inhibitor: A Potential Combination Strategy With Immunotherapy in Cancer","volume":"11","year":"2021","journal-title":"Front. Oncol"},{"key":"2023052412500721000_2023.05.22.541644v1.77","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1038\/s41423-021-00726-4","article-title":"Dendritic cell migration in inflammation and immunity","volume":"18","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"2023052412500721000_2023.05.22.541644v1.78","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0162-3"},{"key":"2023052412500721000_2023.05.22.541644v1.79","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)92168-2"},{"key":"2023052412500721000_2023.05.22.541644v1.80","doi-asserted-by":"crossref","unstructured":"Ko, K. I. et al. Distinct fibroblast progenitor subpopulation expedites regenerative mucosal healing by immunomodulation. J. Exp. Med. 220, (2023).","DOI":"10.1084\/jem.20221350"},{"key":"2023052412500721000_2023.05.22.541644v1.81","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-017-0298-5"},{"key":"2023052412500721000_2023.05.22.541644v1.82","doi-asserted-by":"publisher","DOI":"10.3791\/59666"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.05.22.541644","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:41:08Z","timestamp":1768452068000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.05.22.541644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,22]]},"references-count":82,"URL":"https:\/\/doi.org\/10.1101\/2023.05.22.541644","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1038\/s41467-024-45034-3","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2023,5,22]]},"subtype":"preprint"}}