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

Ayano Fukushima-Nomura, Hiroshi Kawasaki, Kiyoshi Yashiro, Shoko Obata, Keiji Tanese, Tamotsu Ebihara, Hidehisa Saeki, Takafumi Etoh, Takehiro Hasegawa, Junshi Yazaki, Jun Seita, Osamu Ohara, Aiko Sekita, Tomohiro Miyai, Koichi Ashizaki, Haruhiko Koseki, Kazuhiro Sakurada, Eiryo Kawakami () and Masayuki Amagai ()
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Ayano Fukushima-Nomura: Keio University School of Medicine
Hiroshi Kawasaki: Keio University School of Medicine
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)
Jun Seita: RIKEN
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
Haruhiko Koseki: RIKEN Center for Integrative Medical Sciences (IMS)
Kazuhiro Sakurada: RIKEN
Eiryo Kawakami: RIKEN
Masayuki Amagai: Keio University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-22

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-59340-x

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