Elucidation of psoriasis pathogenesis through intra-vital imaging

• Project/Area Number: 15K09766
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kyoto University
• Principal Investigator: Honda Tetsuya 京都大学, 医学研究科, 講師 (40452338)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 乾癬 / 脂質メディエーター / トロンボキサン / ガンマデルタT細胞 / gamma delta T細胞 / IL-17 / 樹状細胞

Outline of Final Research Achievements

Psoriasis is one of the most common, chronic inflammatory skin diseases of unknown etiology. Through intra-vital imaging technique, we analyzed the pathophysiology of psoriasis by using a mouse psoriasis model. We identified close interaction between dendritic cells and gamma delta T cells in the skin. We also identified that thromboxane and leukotriene act on gamma delta T cells and dendritic cells, and promote psoriatic dermatitis in mice. Regulation of these factors may become a therapeutic target for psoriasis.

Academic Significance and Societal Importance of the Research Achievements

トロンボキサンやロイコトリエンは脂質メディエーターと呼ばれる一群の物質です。古くから様々な脂質メディエーターが乾癬病変部で上昇していることが知られていましたが、どれが一体どのような作用をしているかなど、ほとんど不明でした。本研究によりそれらの一端が解明されました。またそれらの脂質メディエーターをターゲットとした、新たな乾癬治療戦略に展開することが期待されます。

Research Products

• [Journal Article] Resolvin E1 attenuates murine psoriatic dermatitis (2018)
  • Author(s): Sawada Yu、Honda Tetsuya、Nakamizo Satoshi、Otsuka Atsushi、Ogawa Narihito、Kobayashi Yuichi、Nakamura Motonobu、Kabashima Kenji
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 1-9
  • DOI: 10.1038/s41598-018-30373-1
  • NAID: 120006539571
  • Peer Reviewed / Open Access
• [Journal Article] Thromboxane A2 facilitates IL-17A production from Vγ4+ γδ T cells and promotes psoriatic dermatitis in mice. (2018)
  • Author(s): Ueharaguchi Y, Honda T, Kusuba N, Hanakawa S, Adachi A, Sawada Y, Otsuka A, Kitoh A, Dainich T, Egawa G, Nakachima C, Nakajima S, Murata T, Ono S, Arita M, Narumiya S, Miyachi Y, Kabashima K
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: in press Issue: 2 Pages: 680-683.e2
  • DOI: 10.1016/j.jaci.2018.01.054
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] RIPK3 controls keratinocyte activation in a necroptosis-independent manner and promotes psoriatic dermatitis in mice (2017)
  • Author(s): Tetsuya Honda, Osamu Yamamoto MD, Yu Sawada, Gyohei Egawa, Akihiko Kitoh, Atsushi Otsuka, Teruki Dainichi, Saeko Nakajima, Yoshiki Miyachi, Kenji Kabashima
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 5 Issue: 2 Pages: 619-622.e6
  • DOI: 10.1016/j.jaci.2017.02.027
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] hree-dimensional evaluation of subclinical extension of extramammary Paget's disease: Visualization of histological border and its comparison to clinical border. (2016)
  • Author(s): Murata, T. Honda, T. Egawa, G. Kitoh, A. Dainichi, T. Otsuka, A. Nakajima, S. Kore-Eda, S. Kaku, Y. Nakamizo, S. Endo, Y. Fujisawa, A. Miyachi, Y. Kabashima, K
  • Journal Title: British Journal of Dermatology Volume: - Issue: 1 Pages: 229-237
  • DOI: 10.1111/bjd.15282
  • Peer Reviewed
• [Presentation] Identification of resolvin E1, an omega-3 poly-unsaturated fatty acids-derived lipid mediator, as an inhibitor for psoriatic dermatitis by downregulating migration of IL-17A-producing cutaneous γδ T cells and IL-23 production from dendritic cells (2017)
  • Author(s): Honda T
  • Organizer: 47th Annual ESDR Meeting
  • Int'l Joint Research
• [Presentation] Diet in the pathogenesis of psoriasis: a review of recent progress (2016)
  • Author(s): Tetsuya Honda
  • Organizer: 第41回日本研究皮膚科学会
  • Place of Presentation: 仙台国際センター(宮城県仙台市）
  • Year and Date: 2016-12-09
  • Invited
• [Presentation] High fat diet exacerbates psoriatic dermatitis by facilitating IL-17-producing gdT cell accumulation in the skin (2016)
  • Author(s): Tetsuya Honda
  • Organizer: SID2016 Society of Investigative Dermatology Annual Meeting
  • Place of Presentation: Scottsdale(米国）
  • Year and Date: 2016-05-11
  • Int'l Joint Research
• [Book] 炎症と免疫 (2017)
  • Author(s): 本田哲也
  • Total Pages: 83
  • Publisher: 先端医学社