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. 2025 Jun 11:S0091-6749(25)00626-8.
doi: 10.1016/j.jaci.2025.06.002. Online ahead of print.

Transcriptomic profiling of vitiligo patients shows polar immune dysregulation in involved and uninvolved skin

Patrick M Brunner  1 , Eden David  1 , Ester Del Duca  2 , Meredith Manson  1 , Agata Kurowski  1 , Malini P Naidu  1 , Lauren R Port  1 , Jesus Gay-Mimbrera  3 , Pedro J Gómez-Arias  4 , Natalia Alkon  5 , Jessica Beaziz-Tordjman  1 , Yeriel Estrada  1 , Yael Renert-Yuval  6 , Juan Ruano  4 , Emma Guttman-Yassky  7
Affiliations

Transcriptomic profiling of vitiligo patients shows polar immune dysregulation in involved and uninvolved skin

Patrick M Brunner et al. J Allergy Clin Immunol. .

Abstract

Background: Vitiligo is a chronic autoimmune skin depigmenting disorder, with a major impact on quality of life. Therapeutic options are still limited, with only one topical JAK inhibitor being approved by the US Food and Drug Administration. Although vitiligo is primarily regarded as a TH1/interferon-driven disease, emerging evidence suggests the involvement of additional immune axes, but their relevance to disease pathogenesis remains unclear.

Objective: We sought to obtain a global cutaneous transcriptomic profile of lesional and nonlesional vitiligo.

Methods: We performed bulk RNA sequencing combined with real-time PCR and immunohistochemistry of skin biopsy samples from 15 lesional and nonlesional vitiligo samples and compared them to 14 matched healthy controls. Results were corroborated by single-cell RNA sequencing.

Results: Robust inflammatory dysregulation was captured not only in lesional but also nonlesional vitiligo skin relative to healthy controls. Lesional samples demonstrated upregulation of TH1 (OASL, CXCL9, CXCL10), TH2 (IL4, IL4R, CCL13, CCL17, CCL22, CCL26), and TH17/22 (IL20, S100A7, S100A8, S100A9, PI3) related markers. Similarly, nonlesional samples demonstrated activation of TH1 (CXCL9, OASL), TH2 (IL4R, IL10, CCL13, CCL17, CCL22), and TH17/22 (PI3, DEFB4A) associated markers. Clinical severity scores (Vitiligo Area Scoring Index and/or Vitiligo Disease Activity Index) significantly and positively correlated with multiple inflammatory mediators (ie, CXCL14, IL25, IL17RC) in lesional and/or nonlesional vitiligo skin. On a single-cell level, IL13 and IFNG expression were primarily found in nonlesional helper T cells and in lesional proliferating T cells, respectively.

Conclusions: Our findings show that immune dysregulation in vitiligo involves immune axes beyond TH1/Tc1, with particular upregulation of type 2 markers already observed in nonlesional skin, suggesting a role during early lesion formation.

Keywords: RNA sequencing; T(H)2; Vitiligo; melanogenesis; scRNA-Seq; skin biomarkers.

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Conflict of interest statement

Disclosure statement Supported by a research grant to PMB from the American Skin Association. E.D. was supported by an ASA Medical Student Grant in Vitiligo. The Omics datalink is available at the Gene Expression Omnibus (GEO; www.ncbi.nlm.nih.gov/geo) under accession no. GSE298871. Disclosure of potential conflict of interest: E. Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to institution) from AbbVie, Celgene, Eli Lilly, Janssen, Medimmune/AstraZeneca, Novartis, Pfizer, Regeneron, Vitae, Glenmark, Galderma, Asana, Innovaderm, Dermira, and UCB; and is a consultant for Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, AnaptysBio, Dermira, Galderma, Glenmark, Novartis, Pfizer, Vitae, Leo Pharma, AbbVie, Eli Lilly, Kyowa, Mitsubishi Tanabe, Asana Biosciences, and Promius. P. M. Brunner has received personal fees from Almirall, Sanofi, Janssen, LEO Pharma, AbbVie, Pfizer, Boehringer Ingelheim, GSK, Regeneron, Eli Lilly, Celgene, Novartis, UCB, Merck, RAPT Therapeutics, Galderma, and BMS; has received research support from Pfizer (grant paid to institution); and is an investigator for Pfizer and AbbVie. The rest of the authors declare that they have no relevant conflicts of interest.

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