Optimal ultraviolet wavelength for immune regulation and development of ultraviolet-LED phototherapy

• Project/Area Number: 17H04242
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Nagoya 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)
• Co-Investigator(Kenkyū-buntansha): 山崎 小百合 名古屋市立大学, 医薬学総合研究院(医学), 教授 (70567255)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2017: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
• Keywords: 紫外線 / 免疫制御 / 制御性Ｔ細胞 / 光線治療 / LED / 光線療法 / 制御性T細胞

Outline of Final Research Achievements

Wavelength analysis to induce iTreg showed inhibition of delayed-type hypersensitivity and induction of Treg at 310 nm and induction of nTreg at 290-300 nm. Demethylation in Treg-related genes leads to Tregs with stable inhibitory functions. The decreased ability to suppress Treg in patients with psoriasis returned to almost normal after phototherapy, indicating that phototherapy restored Treg function. Regarding the induction of Treg in human skin lesions, we succeeded in FACS analysis from a small amount of whole blood collected as lesional blood and in the separation of CD4/CD8 by high-speed cell sorter. We also succeeded in the separation of regulatory T cells.

Academic Significance and Societal Importance of the Research Achievements

今回の研究成果は、光線療法のメカニズムの一部を明らかにするとともに、乾癬の病態がより明確になることが期待される。またTh17細胞がその病態に関与していると考えられている自己免疫性脳脊髄炎（多発性硬化症）や様々な自己免疫疾患に対し光線療法が応用できる可能性があり、今回の研究がその足がかりとなる可能性がある。

Research Products

• [Journal Article] Optimum wavelength characteristics for phototherapy using deep ultraviolet light-emitting diodes (2019)
  • Author(s): Hideyuki Masuda, Makoto Kimura, Akimichi Morita
  • Journal Title: J Dermatol Sci Volume: 93 Issue: 3 Pages: 186-188
  • DOI: 10.1016/j.jdermsci.2019.01.006
  • Peer Reviewed / Open Access
• [Journal Article] Hyperglycemia is associated with psoriatic inflammation in both humans and mice (2019)
  • Author(s): Ikumi K, Odanaka M, Shime H, Imai M, Osaga S, Taguchi O, Nishida E, Hemmi H, Kaisho T, Morita A, Yamazaki S
  • Journal Title: Journal of Investigative Dermatology Volume: 印刷中 Issue: 6 Pages: 1329-1338
  • DOI: 10.1016/j.jid.2019.01.029
  • Peer Reviewed / Open Access
• [Journal Article] Ultraviolet B?Induced Maturation of CD11b-Type Langerin?Dendritic Cells Controls the Expansion of Foxp3+Regulatory T Cells in the Skin (2017)
  • Author(s): Yamazaki Sayuri、Odanaka Mizuyu、Nishioka Akiko、Kasuya Saori、Shime Hiroaki、Hemmi Hiroaki、Imai Masaki、Riethmacher Dieter、Kaisho Tsuneyasu、Ohkura Naganari、Sakaguchi Shimon、Morita Akimichi
  • Journal Title: The Journal of Immunology Volume: 200 Issue: 1 Pages: 119-129
  • DOI: 10.4049/jimmunol.1701056
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Bath-PUVA therapy improves impaired resting regulatory T cells and increases activated regulatory T cells in psoriasis (2017)
  • Author(s): Ryoji Kubo, Shinnosuke Muramatsu, Yoko Sagawa, Chiyo Saito, Saori Kasuya, Akiko Nishioka, Emi Nishida, Sayuri Yamazaki, Akimichi Morita
  • Journal Title: Journal of Dermatological Science Volume: 86 Issue: 1 Pages: 46-53
  • DOI: 10.1016/j.jdermsci.2017.01.001
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Skin dendritic cells expressing a unique set of genes associated with immunological tolerance are specialized to expand thymus-derived Foxp3+ regulatory T cells upon ultraviolet B exposure. (2019)
  • Author(s): Sayuri Yamazaki, Mizuyu Odanaka, Hiroaki Shime, Masaki Imai, Hiroaki Hemmi, Tsuneyasu Kaisho, Naganari Ohkura, Shimon Sakaguchi, and Akimichi Morita
  • Organizer: Japan-Sigapore International Skin Conference 2019
  • Int'l Joint Research
• [Presentation] Wavelength characteristics on application of deep ultraviolet light-emitting diodes to phototherapy (2019)
  • Author(s): Hideyuki Masuda, Makoto Kimura, Akimichi Morita
  • Organizer: Society of Investigative Dermatology
  • Int'l Joint Research
• [Presentation] Dermal dendritic cells present neo-self antigens induced by ultraviolet B exposure to expand Foxp3+ regulatory T cells (2019)
  • Author(s): Sayuri Yamazaki, Mizuyu Odanaka, Hiroaki Shime, Masaki Imai, Hiroaki Hemmi, Tsuneyasu Kaisho, Naganari Ohkura, Shimon Sakaguchi, Akimichi Morita
  • Organizer: Society of Investigative Dermatology
  • Int'l Joint Research
• [Presentation] Dual wavelength photodynamic therapy using a flexible light-emitting diode unit (2019)
  • Author(s): Akimichi Morita
  • Organizer: Society of Investigative Dermatology
  • Int'l Joint Research
• [Presentation] UVA1 phototherapy with suppressed immediate pigment darkening by selective wavelength irradiation (2019)
  • Author(s): Hideyuki Masuda and Akimichi Morita
  • Organizer: ESDR2019
  • Int'l Joint Research
• [Presentation] New immunological aspects of phototherapy for refractory skin diseases (2019)
  • Author(s): Akimichi Morita
  • Organizer: 4th Chinese Society of Investigative Dermatology Annual Meeting
  • Int'l Joint Research
• [Presentation] Regulatory T cells with a distinctive feature expand through dermal dendritic cells in the ultraviolet B exposed skin (2019)
  • Author(s): Sayuri Yamazaki, Mizuyu Odanaka, Hiroaki Shime, Masaki Imai, Hiroaki Hemmi, Tsuneyasu Kaisho, Naganari Ohkura, Shimon Sakaguchi, Akimichi Morita
  • Organizer: 16th international workshop on Langerhans cells
  • Int'l Joint Research
• [Presentation] UVA1 phototherapy with suppressed immediate pigment darkening by selective wavelength irradiation (2019)
  • Author(s): Hideyuki Masuda and Akimichi Morita
  • Organizer: 44th Annual Meeting of the Japanese Society for Investigative Dermatology
• [Presentation] UVA1 phototherapy for the treatment of T cell mediated skin diseases and scleroderma (2019)
  • Author(s): Akimichi Morita
  • Organizer: 45th annual meeting of TDA
  • Int'l Joint Research
• [Presentation] Dual wavelength photodynamic therapy using a flexible light-emitting diode unit (2019)
  • Author(s): Akimichi Morita
  • Organizer: 14th annal meeting of TSID
  • Int'l Joint Research
• [Presentation] New aspects of Phototherapy (2018)
  • Author(s): Akimichi Morita
  • Organizer: 13th meeting of German-Japanese Society for Dermatology
  • Int'l Joint Research
• [Presentation] Regulatory T cell induction prolongs the effiecay for the treatment of psoriasis (2018)
  • Author(s): Akimichi Morita
  • Organizer: Psoriasis syopsium in Thammasat University
  • Int'l Joint Research
• [Presentation] New aspects of phototherapy (2018)
  • Author(s): Akimichi Morita
  • Organizer: TSID
  • Int'l Joint Research
• [Presentation] Wavelength specific gene expression clustering identified by Cap Analysis of Gene Expression in normal human epidermal melanocytes (2017)
  • Author(s): Hideyuki Masuda, Makoto Kimura, Akimichi Morita
  • Organizer: 2017 SID annual meeting, April 26-29, 2016, Portland
  • Int'l Joint Research
• [Presentation] Quantifying of serum IL-17A and TNFa to estimate the formation of psoriatic skin (2017)
  • Author(s): Emi Nishida, Kan Torii, Saori Kasuya, Akiko Nishioka, Kyoko Ikumi, Shinnosuke Muramatsu, Akimichi Morita
  • Organizer: PASI formula, 2017 SID annual meeting, April 26-29, 2016, Portland
  • Int'l Joint Research
• [Presentation] Serum TNF-α levels in patients with psoriasis treated with biologics (2017)
  • Author(s): Shinnosuke Muramatsu, Emi Nishida, Ryoji Kubo, Akimichi Morita
  • Organizer: 2017 SID annual meeting, April 26-29, 2016, Portland
  • Int'l Joint Research
• [Presentation] Sacroiliitis susceptibility of psoriatic arthritis in Asian associates with HLA B46 (2017)
  • Author(s): Kyoko Ikumi, Emi Nishida, Akimichi Morita
  • Organizer: 2017 SID annual meeting, April 26-29, 2016, Portland
  • Int'l Joint Research
• [Presentation] Comparative transcriptome analysis in normal human keratinocytes irradiated with monochromatic UVB wavelength (2017)
  • Author(s): Kan Torii, Akimichi Morita
  • Organizer: 2017 SID annual meeting, April 26-29, 2016, Portland
  • Int'l Joint Research
• [Presentation] Phototherapy and future development for Dermatology (2017)
  • Author(s): Akimichi Morita
  • Organizer: The 1st CICM Academic Meeting“Translation Research: From Bench to Bedside”,August 28, 2017, Thailand
  • Int'l Joint Research
• [Presentation] Wavelength specific gene expression identified by Cap Analysis of Gene Expression in normal human dermal fibroblasts. (2017)
  • Author(s): Hideyuki Masuda, Makoto Kimura, Akimichi Morita
  • Organizer: 47th Annual ESDR meeting, 27-30 September, 2017, Salzburg
• [Presentation] Photochemotherapy limits Treg plasticity and restores Treg function in psoriasis patients. (2017)
  • Author(s): Kan Torii, Ryoji Kubo, Takuya Furuhashi, Shinnosuke Muramatsu, Yoko Sagawa, Chiyo Saito, Sayuri Yamazaki, Akimichi Morita
  • Organizer: 47th Annual ESDR meeting, 27-30 September, 2017, Salzburg (Poster work)
  • Int'l Joint Research
• [Presentation] The influence of photoirradiation on the circadian clock genes in human keratinocyte and melanocyte. (2017)
  • Author(s): Shinnosuke Muramatsu, Kan Torii, Hideyuki Masuda, Akimichi Morita
  • Organizer: 47th Annual ESDR meeting, 27-30 September, 2017, Salzburg (Poster work)
  • Int'l Joint Research
• [Presentation] HLA-B46 associates with sacroiliitis susceptibility in patients with psoriatic arthritis. (2017)
  • Author(s): Kyoko Ikumi, Emi Nishida, Akimichi Morita
  • Organizer: 47th Annual ESDR meeting, 27-30 September, 2017, Salzburg (Poster work)
  • Int'l Joint Research
• [Presentation] The critical role of dendritic cell subset in expanding Foxp3+ regulatory T cells in the murine skin after ultraviolet B exposure. (2017)
  • Author(s): Sayuri Yamazaki, Akiko Nishioka, Saori Kasuya, Mizuyu Odanaka, Hiroaki Hemmi, Masaki Imai, Dieter Riethmacher, Tsuneyasu Kaisho, Naganari Ohkura, Shimon Sakaguchi, Akimichi Morita
  • Organizer: 5th International Workshop on Langerhans cell. 6-8 October, 2017, New York (Oral)
  • Int'l Joint Research
• [Presentation] Phototherapy and future development for Dermatology (2017)
  • Author(s): Akimichi Morita
  • Organizer: Emirates Derma 2017, Nov 2 2017, Abu Dhabi. UAE
  • Int'l Joint Research