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Ruxolitinib Alleviates Inflammation and Fortifies Skin Barrier Function Through Dampening IL-13

Lookup NU author(s): Professor John Common

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Abstract

© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Atopic dermatitis (AD) is a prevalent inflammatory skin disorder characterized by an impaired skin barrier, dysregulated immune system and pruritis. Emerging pharmaceutical therapies for AD include selective Janus kinase (JAK) inhibitors such as ruxolitinib, the first dual JAK1/JAK2 inhibitor approved by the US Food and Drug Administration. This study aimed to evaluate the effects of ruxolitinib on AD-related symptoms using mouse and human skin models. AD-related symptoms were assessed in MC903/ruxolitinib-treated mice, including ear swelling, histological analysis, pruritus, serum biomarker quantification and immune cell analysis. Additionally, immunohistochemistry and transcriptome analysis were conducted on AD-related cytokine-treated reconstructed human skin (RHS) and ruxolitinib-treated human skin explants with and without tape-stripping. Ruxolitinib-treated mice exhibited reduced inflammation, including decreased ear swelling and diminished pruritus. Furthermore, reductions in immune cell populations, including T cells and serum biomarker IL-13, were observed in ruxolitinib-treated mice. Transcriptome analysis revealed increased STAT3 expression and decreased skin barrier gene FLG in AD-related cytokine-treated RHS. Regardless of tape stripping, ruxolitinib-treated skin explants exhibited decreased IL13RA1 expression and increased expression of skin barrier genes FLG, FLG2 and LOR. Ruxolitinib treatment in mice resulted in decreased inflammation and pruritus, along with increased expression of skin barrier proteins through downregulation of IL-13. Consistently, ruxolitinib-treated human skin explants demonstrated enhanced expression of skin barrier proteins, while IL-13 treatment of RHS led to downregulation of these proteins. These findings support data from human clinical trials indicating reduced SCORAD, pruritus and inflammatory phenotypes in AD patients treated with ruxolitinib.

Publication metadata

Author(s): Koh LF, Firdaus MJ, Natsuaki Y, Hanakawa S, Tham K-C, Lunny DP, Yap BLH, Nakamizo S, Nam E, Lee JE, Toh YX, Teo NMH, Lim TC, Lane EB, Kabashima K, Janela B, Common JE

Publication type: Article

Publication status: Published

Journal: Experimental Dermatology

Year: 2025

Volume: 34

Issue: 7

Print publication date: 01/07/2025

Online publication date: 18/07/2025

Acceptance date: 22/06/2025

ISSN (print): 0906-6705

ISSN (electronic): 1600-0625

Publisher: John Wiley and Sons Inc

URL: https://doi.org/10.1111/exd.70132

DOI: 10.1111/exd.70132

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