2. Academic Validation
  3. Ruxolitinib Alleviates Inflammation and Fortifies Skin Barrier Function Through Dampening IL-13

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

  • Exp Dermatol. 2025 Jul;34(7):e70132. doi: 10.1111/exd.70132.
Li Fang Koh 1,  Muhammad Jasrie Firdaus 1,  Yohei Natsuaki 1,  Sho Hanakawa 1 2,  Khek-Chian Tham 1 3,  Declan P Lunny 1 3,  Belle L H Yap 1,  Satoshi Nakamizo 2,  Eori Nam 4,  Ji Eun Lee 4,  Ying Xiu Toh 3,  Nelson M H Teo 5,  Thiam Chye Lim 5,  E Birgitte Lane 1 3,  Kenji Kabashima 1 2 3 6,  Baptiste Janela 1 3 7 8 9,  John E Common 1 3 10
Affiliations

Affiliations

  • 1 A*STAR Skin Research Labs (A*SRL), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • 2 Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • 3 Skin Research Institute of Singapore (SRIS), Singapore, Singapore.
  • 4 JW C&C Research Laboratories, Seoul, Republic of Korea.
  • 5 Department of Plastic, Reconstructive and Aesthetic Surgery, National University Hospital (NUH), Singapore.
  • 6 Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • 7 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
  • 8 A*STAR Infectious Diseases Labs (ID Labs), Agency for Science, Technology and Research (A*STAR), Singapore.
  • 9 National Skin Centre, National Healthcare Group, Singapore.
  • 10 Translational and Clinical Research Institute and NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, England, United Kingdom.
PMID: 40678986 DOI: 10.1111/exd.70132
Abstract

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.

Keywords

JAK/STAT; MC903; atopic dermatitis; reconstructed human skin; ruxolitinib; skin explants.

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