Ito, Yoshihiro

写真a

Affiliation

School of Medicine, Department of Dermatology （Shinanomachi）

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)

Contact Address

東京都新宿区信濃町35東校舎3階
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Licenses and Qualifications 【 Display / hide 】

  • 医師免許, 日本皮膚科学会専門医, 2017.10

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Research Areas 【 Display / hide 】

  • Life Science / Bacteriology

  • Life Science / Immunology

  • Life Science / Dermatology

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Research Keywords 【 Display / hide 】

  • Microbiome

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Research Themes 【 Display / hide 】

  • 皮膚マイクロバイオーム, 

    2015.04
    -
    Present

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Papers 【 Display / hide 】

  • 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.

  • Gene-specific somatic epigenetic mosaicism of FDFT1 underlies a non-hereditary localized form of porokeratosis

    Saito S., Saito Y., Sato S., Aoki S., Fujita H., Ito Y., Ono N., Funakoshi T., Kawai T., Suzuki H., Sasaki T., Tanaka T., Inoie M., Hata K., Kataoka K., Kosaki K., Amagai M., Nakabayashi K., Kubo A.

    American Journal of Human Genetics （American Journal of Human Genetics)  111 （ 5 ） 896 - 912 2024.05

    ISSN  00029297

    　View Summary

    Porokeratosis is a clonal keratinization disorder characterized by solitary, linearly arranged, or generally distributed multiple skin lesions. Previous studies showed that genetic alterations in MVK, PMVK, MVD, or FDPS—genes in the mevalonate pathway—cause hereditary porokeratosis, with skin lesions harboring germline and lesion-specific somatic variants on opposite alleles. Here, we identified non-hereditary porokeratosis associated with epigenetic silencing of FDFT1, another gene in the mevalonate pathway. Skin lesions of the generalized form had germline and lesion-specific somatic variants on opposite alleles in FDFT1, representing FDFT1-associated hereditary porokeratosis identified in this study. Conversely, lesions of the solitary or linearly arranged localized form had somatic bi-allelic promoter hypermethylation or mono-allelic promoter hypermethylation with somatic genetic alterations on opposite alleles in FDFT1, indicating non-hereditary porokeratosis. FDFT1 localization was uniformly diminished within the lesions, and lesion-derived keratinocytes showed cholesterol dependence for cell growth and altered expression of genes related to cell-cycle and epidermal development, confirming that lesions form by clonal expansion of FDFT1-deficient keratinocytes. In some individuals with the localized form, gene-specific promoter hypermethylation of FDFT1 was detected in morphologically normal epidermis adjacent to methylation-related lesions but not distal to these lesions, suggesting that asymptomatic somatic epigenetic mosaicism of FDFT1 predisposes certain skin areas to the disease. Finally, consistent with its genetic etiology, topical statin treatment ameliorated lesions in FDFT1-deficient porokeratosis. In conclusion, we identified bi-allelic genetic and/or epigenetic alterations of FDFT1 as a cause of porokeratosis and shed light on the pathogenesis of skin mosaicism involving clonal expansion of epigenetically altered cells.

  • Apremilast is a potentially useful treatment for severe palmoplantar pustulosis with extra-palmoplantar symptoms

    Fukushima-Nomura A., Takamiyagi S., Kakuta R., Ito Y., Hirai I., Umemoto J., Hanaoka H., Kaneko Y., Tanese K.

    Skin Health and Disease （Skin Health and Disease)  4 （ 2 ）  2024.04

    　View Summary

    Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disorder affecting the palms and soles. In rare cases, severe patients develop acute extra-palmoplantar lesions often accompanied by arthralgia. Such cases with extensive symptoms often necessitate systemic treatments with variable efficacy and potential side effects. Apremilast, known for its broad immune response modulation, presents promise as a therapeutic option for severe PPP with joint and extra-palmoplantar lesions. This case highlights apremilast as a potential systemic treatment for such cases with minimal side effects.

  • Dissecting skin microbiota and microenvironment for the development of therapeutic strategies

    Ito Y., Amagai M.

    Current Opinion in Microbiology （Current Opinion in Microbiology)  74 2023.08

    ISSN  13695274

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    The skin is a pivotal barrier between the human body and the environment, and is a habitat for numerous microorganisms. While host–microbiota interactions in the skin are essential for homeostasis, disturbances in microbial composition and the abnormal growth of certain bacteria are associated with various diseases. Here, we identify strains and communities of skin commensals that contribute to or impair skin barrier function. Furthermore, we discuss the skin microenvironments suitable for specific microbiota that exert therapeutic effects and suggest focus areas for the prospective development of therapeutic strategies using bacterial agents. Finally, we highlight recent efforts to treat skin diseases associated with live bacteria.

  • Controlling skin microbiome as a new bacteriotherapy for inflammatory skin diseases

    Ito Y., Amagai M.

    Inflammation and Regeneration （Inflammation and Regeneration)  42 （ 1 ）  2022.12

    　View Summary

    The skin serves as the interface between the human body and the environment and interacts with the microbial community. The skin microbiota consists of microorganisms, such as bacteria, fungi, mites, and viruses, and they fluctuate depending on the microenvironment defined by anatomical location and physiological function. The balance of interactions between the host and microbiota plays a pivotal role in the orchestration of skin homeostasis; however, the disturbance of the balance due to an alteration in the microbial communities, namely, dysbiosis, leads to various skin disorders. Recent developments in sequencing technology have provided new insights into the structure and function of skin microbial communities. Based on high-throughput sequencing analysis, a growing body of evidence indicates that a new treatment using live bacteria, termed bacteriotherapy, is a feasible therapeutic option for cutaneous diseases caused by dysbiosis. In particular, the administration of specific bacterial strains has been investigated as an exclusionary treatment strategy against pathogens associated with chronic skin disorders, whereas the safety, efficacy, and sustainability of this therapeutic approach using isolated live bacteria need to be further explored. In this review, we summarize our current understanding of the skin microbiota, as well as therapeutic strategies using characterized strains of live bacteria for skin inflammatory diseases. The ecosystem formed by interactions between the host and skin microbial consortium is still largely unexplored; however, advances in our understanding of the function of the skin microbiota at the strain level will lead to the development of new therapeutic methods.

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  • 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

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