KEIO RESEARCHERS INFORMATION SYSTEM

Licenses and Qualifications 【 Display / hide 】

Licenses and Qualifications 【 Display / hide 】

• 医師免許, 日本皮膚科学会専門医, 2017.10

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Bacteriology

• Life Science / Immunology

• Life Science / Dermatology

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• Microbiome

Research Themes 【 Display / hide 】

Research Themes 【 Display / hide 】

• 皮膚マイクロバイオーム, 

  2015.04

  -

  Present

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Microbial dysbiosis and foot odor in Nagashima-type palmoplantar keratosis: Improvement with topical benzoyl peroxide

  Ono N., Ito Y., Aoki S., Shiohama A., Sasaki T., Kurokawa R., Suda W., Amagai M., Kubo A.

  Journal of Investigative Dermatology 146 ( 6 ) 1586 - 1595.e5 2026.06

  ISSN  0022202X

  　View Summary

  Nagashima-type palmoplantar keratosis (also referred to as SERPINB7 -related palmoplantar epidermal differentiation disorder) is the most common form of palmoplantar keratoderma in East Asia. It is characterized by erythematous hyperkeratosis, palmoplantar hyperhidrosis, and a distinctive foot odor that significantly impairs QOL. In this study, we aimed to clarify the etiology of this odor by investigating the plantar microbiome and evaluating the therapeutic effects of topical benzoyl peroxide. Compared with healthy controls, individuals with Nagashima-type palmoplantar keratosis exhibited significantly higher objective odor scores; increased bacterial load, especially in the intertoe area; and reduced microbial diversity. Corynebacterium and Staphylococcus were the predominant dysbiotic flora species. The topical application of benzoyl peroxide significantly reduced foot odor and bacterial load; increased microbial diversity; and selectively decreased Corynebacterium abundance, particularly that of C tuberculostearicum . These changes correlate with the species-specific susceptibility of skin-resident bacteria to benzoyl peroxide. Our findings suggest that microbial dysbiosis, especially the overgrowth of Corynebacterium species, is central to the pathogenesis of foot odor in Nagashima-type palmoplantar keratosis. Topical benzoyl peroxide is a promising therapeutic intervention for mitigating dysbiosis and its associated foot odor. This study highlights the potential of microbiome-targeted therapies for symptom relief in inherited skin disorders such as Nagashima-type palmoplantar keratosis.

  • Access to Document (DOI)

• Recurrent familial furunculosis associated with Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus sublineage of the USA300 clone in Tokyo

  Fukushima-Nomura A., Takamiyagi S., Ito Y., Sawada K., Kawasaki H., Sugai M., Hisatsune J.

  Journal of Infection and Chemotherapy 31 ( 12 )  2025.12

  ISSN  1341321X

  　View Summary

  We report a familial case of recurrent furunculosis caused by Panton-Valentine leukocidin (PVL)-positive community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Tokyo. The index case, a 34-year-old female, and her family members (her husband and their 8-month-old son) were also affected, and all recovered after treatment with oral clindamycin, intranasal mupirocin, and hygiene interventions. Whole-genome sequencing revealed that five isolates from skin and nasal swabs belonged to ST8-IVa-t304, carrying ACME type I and PVL genes. All isolates were resistant to levofloxacin but susceptible to other anti-MRSA agents. Genomic analysis showed the absence of the SaPI5 island and the sek/seq genes. Based on phylogenetic analysis, we concluded that these strains represent a unique USA300-like sublineage that diverged from the closest USA300-NAE lineage. The USA300 clone has emerged globally as a dominant CA-MRSA lineage responsible for severe skin and soft tissue infections. In Japan, PVL-positive USA300-related clones have been increasingly identified in recent years, indicating ongoing diversification of community-associated MRSA lineages. This case illustrates the growing presence of USA300-related clones in Japan and the need for genomic surveillance and early intervention to prevent further spread in community settings.

  • Access to Document (DOI)

• Antigen-specific immune responses and microbiota interactions in skin: Insights into autoimmune skin diseases and emerging therapeutic strategies

  Takahashi H., Fukuda K., Ito Y., Amagai M.

  Journal of Allergy and Clinical Immunology 156 ( 3 ) 557 - 567 2025.09

  ISSN  00916749

  　View Summary

  The skin plays a vital role in serving as a physical and immunologic barrier against external insults while orchestrating complex immune responses. Autoimmune skin diseases including pemphigus, vitiligo, and alopecia areata illustrate the intricate interplay between antigen-specific immunity and tissue-specific pathologies. Pemphigus serves as a model to understand the dynamics of peripheral immune tolerance and the interplay between humoral and cellular autoimmunity, emphasizing the role of regulatory T cells in controlling autoreactive responses. Similarly, vitiligo and alopecia areata highlight the pathological contribution of resident memory CD8⁺ T cells and IFN-γ signaling, identifying potential therapeutic targets such as the IL-15 signaling pathway to address disease intractability. In addition to autoimmune mechanisms, the skin microbiota profoundly influences local and systemic immune responses. Commensals such as Staphylococcus epidermidis promote homeostasis by regulating barrier integrity, T-cell activation, and wound repair, while dysbiosis exacerbates immune dysregulation. Innovative strategies, including the use of genetically modified microorganisms to stimulate antigen-specific immunity, hold promise for next-generation therapies. This review underscores the significance of antigen-specific immunity in skin diseases and the emerging role of microbiota in modulating immune responses. Future research into these areas is pivotal for advancing targeted therapies and understanding the interconnectedness of skin health and systemic immunity.

  • Access to Document (DOI)

• Barrier Integrity and Immunity: Exploring the Cutaneous Front Line in Health and Disease

  Fukuda K., Ito Y., Amagai M.

  Annual Review of Immunology 43 ( 1 ) 219 - 252 2025.04

  ISSN  07320582

  　View Summary

  Immune responses are influenced by not only immune cells but also the tissue microenvironment where these cells reside. Recent advancements in understanding the underlying molecular mechanisms and structures of the epidermal tight junctions (TJs) and stratum corneum (SC) have significantly enhanced our knowledge of skin barrier functions. TJs, located in the granular layer of the epidermis, are crucial boundary elements in the differentiation process, particularly in the transition from living cells to dead cells. The SC forms from dead keratinocytes via corneoptosis and features three distinct pH zones critical for barrier function and homeostasis. Additionally, the SC-skin microbiota interactions are crucial for modulating immune responses and protecting against pathogens. In this review, we explore how these components contribute both to healthy and disease states. By targeting the skin barrier in therapeutic strategies, we can enhance its integrity, modulate immune responses, and ultimately improve outcomes for patients with inflammatory skin conditions.

  • Access to Document (DOI)

• Three stepwise pH progressions in stratum corneum for homeostatic maintenance of the skin

  Fukuda K., Ito Y., Furuichi Y., Matsui T., Horikawa H., Miyano T., Okada T., van Logtestijn M., Tanaka R.J., Miyawaki A., Amagai M.

  Nature Communications (Nature Communications)  15 ( 1 )  2024.12

  　View Summary

  The stratum corneum is the outermost skin layer with a vital role in skin barrier function. It is comprised of dead keratinocytes (corneocytes) and is known to maintain its thickness by shedding cells, although, the precise mechanisms that safeguard stratum corneum maturation and homeostasis remain unclear. Previous ex vivo studies have suggested a neutral-to-acidic pH gradient in the stratum corneum. Here, we use intravital pH imaging at single-corneocyte resolution to demonstrate that corneocytes actually undergo differentiation to develop three distinct zones in the stratum corneum, each with a distinct pH value. We identified a moderately acidic lower, an acidic middle, and a pH-neutral upper layer in the stratum corneum, with tight junctions playing a key role in their development. The upper pH neutral zone can adjust its pH according to the external environment and has a neutral pH under steady-state conditions owing to the influence of skin microbiota. The middle acidic pH zone provides a defensive barrier against pathogens. With mathematical modeling, we demonstrate the controlled protease activation of kallikrein-related peptidases on the stratum corneum surface that results in proper corneocyte shedding in desquamation. This work adds crucial information to our understanding of how stratum corneum homeostasis is maintained.

  • Access to Document (DOI)

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Papers, etc., Registered in KOARA 【 Display / hide 】

Papers, etc., Registered in KOARA 【 Display / hide 】

• Identification of novel functions at the strain level in the skin microbiota

  Ito, Yoshihiro

  科学研究費補助金研究成果報告書 2023

• Staphylococcus cohniiは抗炎症作用を有した皮膚常在菌の生物製剤となり得る

  Itō, Yoshihiro

  (慶應義塾大学大学院医学研究科)  2021

• Staphylococcus cohniiは抗炎症作用を有した皮膚常在菌の生物製剤となり得る

  Itō, Yoshihiro

  (慶應義塾大学大学院医学研究科)  2021

• Staphylococcus cohniiは抗炎症作用を有した皮膚常在菌の生物製剤となり得る

  Itō, Yoshihiro

  (慶應義塾大学大学院医学研究科)  2021

Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• A Case of Annular Pustular Psoriasis Possibly Triggered by Cabozantinib and Edoxaban During Nivolumab Therapy

  Nagatake M., Horikawa H., Kakuta R., Adachi T., Fukumoto K., Amagai M., Ito Y.

  Journal of Dermatology 53 ( 7 ) e596 - e598 2026.07

  ISSN  03852407

  • Access to Document (DOI)

• Interleukin-22 and Interleukin-18 as Potential Blood Biomarkers in Dupilumab-Treated Atopic Dermatitis

  Fukushima-Nomura A., Kawasaki H., Hasegawa T., Yanagisawa E., Tanese K., Yanagida N., Obata S., Yashiro K., Ito Y., Koseki H., Amagai M.

  Allergy European Journal of Allergy and Clinical Immunology 81 ( 7 ) 2527 - 2530 2026.07

  ISSN  01054538

  • Access to Document (DOI)

• A Case of Onychocytic Matricoma With Multiple Small Cavities at the Nail Edge: The Clinicopathological Correlation

  Kakuta R., Matsuzaki H., Kawashima Y., Hosokawa R., Hirai I., Ito Y., Ouchi T., Takahashi H., Saito M.

  Journal of Dermatology  2026

  ISSN  03852407

  • Access to Document (DOI)

• AI-Based Objective Severity Assessment of Atopic Dermatitis Using Patient Photos in a Real-World Setting: A Digital Biomarker Approach

  Okata-Karigane U., Hirota M., Takahashi C., Miyagawa A., Ako R., Nakajima S., Futamura M., Yonekura S., Ogawa Y., Inomata T., Ishikawa T., Ito Y., Masaki K., Sato S., Katoh N., Morita H., Adachi T.

  Allergy European Journal of Allergy and Clinical Immunology 80 ( 11 ) 3185 - 3189 2025.11

  ISSN  01054538

  • Access to Document (DOI)

• The Acid Mantle Reimagined: Unveiling the Role of Stepwise pH Zonation in the Stratum Corneum

  Fukuda K., Ito Y., Amagai M.

  Journal of Investigative Dermatology 145 ( 9 ) 2147 - 2152 2025.09

  ISSN  0022202X

  　View Summary

  The stratum corneum (SC), the outermost layer of the skin comprising corneocytes, is essential for maintaining skin barrier function. Although all components of the SC are nonliving, their homeostasis is maintained through the controlled shedding of corneocytes, ensuring a constant number of layers and consistent thickness; however, the mechanisms underlying this regulation remain largely unknown. Although previous studies have suggested a neutral-to-acidic pH gradient in the SC, recent intravital imaging at single-corneocyte resolution revealed a 3-stepwise pH zonation: lower-moderately acidic, middle acidic, and upper neutral. This perspective review highlights the importance of understanding SC homeostasis using this 3-tiered pH model and emphasizes how its disruption may contribute to inflammatory skin diseases. Determination of the mechanisms that establish and maintain these pH zones offers promising insights for the development of targeted therapies.

  • Access to Document (DOI)

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

Research Projects of Competitive Funds, etc. 【 Display / hide 】

• Elucidation of the dynamics and colonization mechanism of skin microbiota in the stratum corneum

  2024.04

  -

  2027.03

  基盤研究(C), Principal investigator

• ヒト皮膚微生物叢における菌株レベルでの新規機能の同定

  2021.04

  -

  2024.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

Awards 【 Display / hide 】

Awards 【 Display / hide 】

• 2025 Young Japanese Society for Investigative Dermatology Award

  2025.12, Japanese Society for Investigative Dermatology

  Type of Award： Award from international society, conference, symposium, etc.

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• LECTURE SERIES, DERMATOLOGY

  2026