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An unbiased tissue transcriptome analysis identifies potential markers for skin phenotypes and therapeutic responses in atopic dermatitis

Author

Listed:
  • Ayano Fukushima-Nomura

    (Keio University School of Medicine)

  • Hiroshi Kawasaki

    (Keio University School of Medicine
    RIKEN Center for Integrative Medical Sciences (IMS))

  • Kiyoshi Yashiro

    (Keio University School of Medicine)

  • Shoko Obata

    (Keio University School of Medicine)

  • Keiji Tanese

    (Keio University School of Medicine)

  • Tamotsu Ebihara

    (Keio University School of Medicine)

  • Hidehisa Saeki

    (Nippon Medical School)

  • Takafumi Etoh

    (Tokyo Teishin Hospital)

  • Takehiro Hasegawa

    (Research and Development Division)

  • Junshi Yazaki

    (RIKEN Center for Integrative Medical Sciences (IMS)
    Setsunan University)

  • Jun Seita

    (RIKEN
    RIKEN Center for Integrative Medical Sciences (IMS))

  • Osamu Ohara

    (Kazusa DNA Research Institute)

  • Aiko Sekita

    (RIKEN Center for Integrative Medical Sciences (IMS))

  • Tomohiro Miyai

    (RIKEN Center for Integrative Medical Sciences (IMS))

  • Koichi Ashizaki

    (Keio University School of Medicine
    RIKEN Center for Integrative Medical Sciences (IMS)
    RIKEN
    RIKEN Center for Integrative Medical Sciences (IMS))

  • Haruhiko Koseki

    (RIKEN Center for Integrative Medical Sciences (IMS)
    Chiba University)

  • Kazuhiro Sakurada

    (RIKEN
    Keio University School of Medicine
    RIKEN Center for Integrative Medical Sciences (IMS))

  • Eiryo Kawakami

    (RIKEN
    Chiba University
    Chiba University
    RIKEN Center for Integrative Medical Sciences (IMS))

  • Masayuki Amagai

    (Keio University School of Medicine
    RIKEN Center for Integrative Medical Sciences (IMS))

Abstract

Atopic dermatitis (AD) is a skin disease exhibiting clinical and molecular heterogeneity, thereby jeopardizing the development of personalized treatments. Here we pursue a cross-sectional and longitudinal cohort analysis of 951 whole-skin samples, employing an unsupervised decomposition analysis to link gene expression profiles to disease severity, six distinct skin phenotypes, and blood cytokines representative of given endotypes. Specifically, type 2 and type 17 responses are associated with major skin phenotypes such as erythema and induration, while type 1 response is upregulated in lichen amyloidosis of AD patients. Longitudinal analysis of patients treated with dupilumab finds sustained gene signatures related to type 17 response in lesional skin and upregulated transcription factors in non-lesional skin of patients with poor treatment outcomes. Lastly, several extracellular matrix organization-associated genes are correlated with clinical severity and treatment response to dupilumab. Our findings thus provide potential skin and blood biomarkers for assessing endotypes and therapeutic responses in AD to pave the way for personalized medicine.

Suggested Citation

  • Ayano Fukushima-Nomura & Hiroshi Kawasaki & Kiyoshi Yashiro & Shoko Obata & Keiji Tanese & Tamotsu Ebihara & Hidehisa Saeki & Takafumi Etoh & Takehiro Hasegawa & Junshi Yazaki & Jun Seita & Osamu Ohar, 2025. "An unbiased tissue transcriptome analysis identifies potential markers for skin phenotypes and therapeutic responses in atopic dermatitis," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59340-x
    DOI: 10.1038/s41467-025-59340-x
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    References listed on IDEAS

    as
    1. Perrine Soret & Christelle Le Dantec & Emiko Desvaux & Nathan Foulquier & Bastien Chassagnol & Sandra Hubert & Christophe Jamin & Guillermo Barturen & Guillaume Desachy & Valérie Devauchelle-Pensec & , 2021. "A new molecular classification to drive precision treatment strategies in primary Sjögren’s syndrome," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    2. Aiko Sekita & Hiroshi Kawasaki & Ayano Fukushima-Nomura & Kiyoshi Yashiro & Keiji Tanese & Susumu Toshima & Koichi Ashizaki & Tomohiro Miyai & Junshi Yazaki & Atsuo Kobayashi & Shinichi Namba & Tatsuh, 2023. "Multifaceted analysis of cross-tissue transcriptomes reveals phenotype–endotype associations in atopic dermatitis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Shuxiong Wang & Michael L. Drummond & Christian F. Guerrero-Juarez & Eric Tarapore & Adam L. MacLean & Adam R. Stabell & Stephanie C. Wu & Guadalupe Gutierrez & Bao T. That & Claudia A. Benavente & Qi, 2020. "Single cell transcriptomics of human epidermis identifies basal stem cell transition states," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
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