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Induction and analysis of regulatory T cells by ultraviolet irradiation - Development of liquid biopsy for skin lesions

Research Project

Project/Area Number 20H03703
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionNagoya City University

Principal Investigator

Morita Akimichi  名古屋市立大学, 医薬学総合研究院(医学), 教授 (30264732)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2023: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2022: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2020: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Keywords紫外線 / 制御性T細胞 / リキッドバイオプシー / 免疫寛容 / 0
Outline of Research at the Start

紫外領域の波長ごとの解析を行い、制御性T細胞 (Treg)の誘導波長はあきらかになりつつある。光線療法後の皮膚病変においてのTregの誘導は組織染色では細胞数も少なく、分離も容易ではなくTregの十分な解析はできない。そこで、皮膚病変の皮疹血リキッドバイオプシー(皮膚生検時の少量の皮疹血の採取)を開発し、どのようなTregが誘導されているか解析を行い、さらにTregの誘導紫外線波長特性の解析も精度上げて行う。100μlの全血サンプルから、十分に解析可能で、高速セルソーターで分離し、シングルセルRNAシークエンス、T細胞レパトア、Treg関連遺伝子のエピジェネティックなどの解析で行う予定である。

Outline of Final Research Achievements

A lesional blood liquid biopsy of cutaneous T-cell lymphoma (CTCL) was performed. CD4+CD45RO+ cells were significantly more abundant in leional blood. mSWAT was inversely correlated with CD8+CD45RO+ cells in lesions. chemokines that induce malignant T cells, such as CCL17 and CCL22, were higher in lesional blood, RNA-seq showed high expression of CTCL tumor cell-specific genes, and TCR repertoire analysis revealed a polarized T-cell receptor. Lesional blood contained skin disease-specific cells and proteins, establishing a technique for lesional blood liquid biopsy. The study of regulatory T cell induction wavelengths revealed that the expression of IL-10 and CCL22 increased 2- to 3-fold in the UVC-UVB wavelengths, and the "Tregness" of CD4-positive T cells was increased by UV irradiation at 260 nm, 280 nm, and 300 nm.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、皮膚疾患の病変の皮疹血から、疾患特異的な細胞やタンパク質を十分に解析することができ、臨床レベルでも他の炎症疾患の診断に役立つ可能性があることが示唆された。臨床レベルにはつなげることはできていないが、制御性T細胞が、UVC~UVBの短い波長で誘導されることもあきらかにし、今後、制御性T細胞の誘導が最適となるような光線療法の開発が、リキッドバイオプシーによって可能になると思われる。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (28 results)

All 2024 2023 2022 2021 2020

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (20 results) (of which Int'l Joint Research: 16 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Cigarette smoking is an independent risk factor for developing vitiligo on the hands. Photodermatology2024

    • Author(s)
      Yuki Enomoto, Yoshifumi Kanayama, Kyoko Ikumi, Mai Sakurai, Aya Yamamoto, Akimichi Morita
    • Journal Title

      Photoimmunology & Photomedicine

      Volume: 40 Issue: 1 Pages: 1-5

    • DOI

      10.1111/phpp.12930

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of mycosis fungoides effectively treated with ultraviolet light A 1-light-emitting diode phototherapy, Photodermatology2023

    • Author(s)
      Kyoko Ikumi, Kan Torii, Tomohiko Kio, Hideyuki Masuda, Yoshifumi Kanayama, Akimichi Morita
    • Journal Title

      Photoimmunology & Photomedicine

      Volume: 39 Issue: 1 Pages: 69-71

    • DOI

      10.1111/phpp.12798

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of actinic lentigines due to multiple sub-erythemal exposure to UVA1 radiation in Asian skin2023

    • Author(s)
      Akimichi Morita, Seite, Sophie; Dantec, Guenaelle Le; Kerob, Delphine
    • Journal Title

      Exp Dermato

      Volume: 32 Issue: 11 Pages: 2034-2037

    • DOI

      10.1111/exd.14937

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Determining the immune environment of cutaneous T‐cell lymphoma lesions through the assessment of lesional blood drops2021

    • Author(s)
      Kan Torii, Yukinori Okada Akimichi Morita
    • Journal Title

      Sci Rep

      Volume: 11 Issue: 1 Pages: 19629-19629

    • DOI

      10.1038/s41598-021-98804-0

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Time kinetics of cyclobutane pyrimidine dimer formation by narrowband and broadband UVB irradiation2021

    • Author(s)
      Erika Toriyama, Hideyuki Masuda, Kan Torii, Kyoko Ikumi, Akimichi Morita
    • Journal Title

      J Dermatol Sci

      Volume: 103 Issue: 3 Pages: 151-155

    • DOI

      10.1016/j.jdermsci.2021.07.009

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successful treatment of UVA1-LED for dyshidrotic palmoplantar eczema2020

    • Author(s)
      Kyoko Ikumi, Tomohiko Kio, Kan Torii, Hideyuki Masuda, Akimichi Morita
    • Journal Title

      J Dermatol

      Volume: 47 Issue: 8 Pages: 922-923

    • DOI

      10.1111/1346-8138.15402

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proenkephalin+regulatory T cells expanded by ultraviolet B exposure maintain skin homeostasis with a healing function2020

    • Author(s)
      Shime Hiroaki、Odanaka Mizuyu、Tsuiji Makoto、Matoba Takuma、Imai Masaki、Yasumizu Yoshiaki、Uraki Ryuta、Minohara Kiyoshi、Watanabe Maiko、Bonito Anthony John、Fukuyama Hidehiro、Ohkura Naganari、Sakaguchi Shimon、Morita Akimichi、Yamazaki Sayuri
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 117 Issue: 34 Pages: 20696-20705

    • DOI

      10.1073/pnas.2000372117

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Effects on Human Skin of Ultraviolet-A1 Irradiation and Development of Actinic Lentigines due to Exposure to UVA1 Radiation2024

    • Author(s)
      Akimichi Morita
    • Organizer
      KSID2024
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ultraviolet A1 phototherapy for the treatment of palmoplantar pustulosis2024

    • Author(s)
      Oki Watanabe1, Yuki Enomoto, Mai Sakurai, Aya Yamamoto, Akimichi Morita
    • Organizer
      KSID 2024
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 紫外線から可視光線の波長特性を利用した光線療法の将来2023

    • Author(s)
      Akimichi Morita
    • Organizer
      第45回光医学・光生物学
    • Related Report
      2023 Annual Research Report
  • [Presentation] Extracorporeal photopheresis with quartz capillary tubes and UVC light emitting diodes does not require photosensitizers and centrifugation2023

    • Author(s)
      Hideyuki Masuda1,2, Akimichi Morita
    • Organizer
      ISID2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of phototherapy on refractory alopecia areata,2023

    • Author(s)
      Aya Yamamoto, Yuki Enomoto, Yoshifumi Kanayama, Mai Sakurai, Kyoko Ikumi, Akimichi Morita
    • Organizer
      ISID2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A large-scale retrospective analysis of a single center study of bath-psoralen plus ultraviolet A (PUVA) therapy for psoriasis2023

    • Author(s)
      Mai Sakurai, Aya Yamamoto , Yuki Enomoto, Yoshifumi Kanayama, Kyoko Ikumi, Akimichi Morita
    • Organizer
      ISID2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] UVC irradiation induces neuropilin-1+ regulatory T cells in skin and lymph nodes2023

    • Author(s)
      Yoshifumi Kanayama, Yoshiaki Yasumizu, Kyoko Ikumi, Yamami Nakamura, Reo Morimoto, Sayuri Yamazaki, Naganari Ohkura, Akimichi Morita
    • Organizer
      ISID2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Basic aspects of phototherapy and underlying mechanisms of photo(chemo)therapy2023

    • Author(s)
      Akimichi Morita
    • Organizer
      2nd Photodermaotlogy 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Phototherapy (Excimer light, narrowband UVB and LED-based, UVA1, and PUVA) for refractory skin diseases2023

    • Author(s)
      Akimichi Morita
    • Organizer
      2nd Photodermaotlogy 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Is PUVA no longer necessary for refractory skin diseases?2023

    • Author(s)
      Akimichi Morita
    • Organizer
      49th annual meeting for Taiwanese Dermatological Association (TDA2023)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] UVC irradiation induces neuropilin-1+ regulatory T cells in skin and lymph nodes2023

    • Author(s)
      Akimichi Morita
    • Organizer
      49th annual meeting for Taiwanese Dermatological Association (TDA2023)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] selective UV spectra for the induction of regulatory T-cells2022

    • Author(s)
      Akimichi Morita
    • Organizer
      Joint ASP-ESP session of the 2022 meeting of the American Society for Photobiology
    • Related Report
      2022 Annual Research Report
  • [Presentation] Bath-PUVA therapy changes inflammatory profiles for systemic effects beyond the skin2022

    • Author(s)
      Yoshifumi Kanayama, Kyoko Ikumi, Kan Torii, Yuki Enomoto, Aya Yamamoto, Akimichi Morita
    • Organizer
      ESDR 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bath-PUVA therapy modulates systemic inflammatory proteomic signatures to lower cardiovascular risk2022

    • Author(s)
      Yoshifumi Kanayama, Kyoko Ikumi, Mai Sakurai, Kan Torii, Yuki Enomoto, Aya Yamamoto, Akimichi Morita
    • Organizer
      47th JSID
    • Related Report
      2022 Annual Research Report
  • [Presentation] UVA1 phototherapy for the treatment of T cell mediated skin diseases and scleroderma2021

    • Author(s)
      Akimichi Morita
    • Organizer
      7th Global Chinese Dermatological Summit
    • Related Report
      2021 Annual Research Report
  • [Presentation] Regulatory T cell induction prolongs the effiecay for the treatment of psoriasis2021

    • Author(s)
      Akimichi Morita
    • Organizer
      19th European Society of photobiology Congress,
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Skin liquid biopsy method for assessing the immune environment of cutaneous T-cell lymphoma lesions2021

    • Author(s)
      Kan Torii, Yukinori Okada, Akimichi Morita
    • Organizer
      50th European Society of Dermatological Research
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Suitable wavelength characteristics for applying deep ultraviolet light-emitting diodes to phototherapy2021

    • Author(s)
      Hideyuki Masuda, Akimichi Morita
    • Organizer
      50th European Society of Dermatological Research
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Role of phototherapy in the management of psoriasis.2021

    • Author(s)
      Akimchi Morita
    • Organizer
      International Psoriasis Council, Psoriasis Masterclass
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Phototherapy basics and treatment tips2020

    • Author(s)
      Akimichi Morita
    • Organizer
      The 46th Annual Meeting of the Taiwanese Dermatological Association (TDA)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 制御性T細胞を誘導するための紫外線照射装置及び制御性T細胞の製造方法2023

    • Inventor(s)
      森田明理、金山佳史
    • Industrial Property Rights Holder
      森田明理、金山佳史
    • Industrial Property Rights Type
      特許
    • Filing Date
      2023
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2025-01-30  

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