Possible roles of immune cells and sensory nerve communication in atopic dermatitis

• Project/Area Number: 17H07096
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: Juntendo University
• Principal Investigator: Toyama Sumika 順天堂大学, 医学(系)研究科(研究院), 博士研究員 (50805893)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: アトピー性皮膚炎 / 難治性痒み / 好酸球 / 神経線維 / 免疫細胞 / Th2 / 知覚神経 / ILC2 / 痒み / かゆみ / アレルギー / 自然リンパ球

Outline of Final Research Achievements

In this study, we investigated that interaction between immune cells and sensory nerves, and to find new therapy targets for itch in atopic dermatitis (AD). As a result, B cells and regulatory T cells (Treg) number was decreased in NC/Nga mouse, an AD model. In addition, eosinophils migrated to lesional skin of AD model mice and patients. Moreover, eosinophils contacted to sensory nerves at eosinophils co-culture with sensory nerves. Therefore, this finding suggest that eosinophils may be new target for itch in AD.

Academic Significance and Societal Importance of the Research Achievements

かゆみは『掻破したいという欲望を起こさせる不快な感覚』として定義されており、近年では外部異物に対する自己防衛反応や全身の異常を知らせる警告（アラーム）として考えられている。知覚異常としてのかゆみは、痛みと同様にQOL(qualityoflife)を著しく低下させる。特に、既存治療が無効な難治性のかゆみは不眠、自殺率（願望）の増加、労働・勉学障害等の一因となっており、世界中で難治性かゆみの新規治療法の開発が進められている。
本研究成果により、ADにおける好酸球の新規制御法の開発及び好酸球を標的とした新規痒み治療法の開発に繋がると考えられ、大変意義がある。

Research Products

• [Journal Article] Liver transplantation: New treatment for mucopolysaccharidosis type VI in rats. (2019)
  • Author(s): Toyama S, Migita O, Fujino M, Kunieda T, Kosuga M, Fukuhara Y, Nagahara Y, Li XK, Okuyama T.
  • Journal Title: Pediatr Int Volume: 261 Issue: 2 Pages: 180-189
  • DOI: 10.1111/ped.13751
  • Peer Reviewed / Open Access
• [Journal Article] Chitin promotes antigen-specific Th2 cell-mediated murine asthma through induction of IL-33-mediated IL-1β production by DCs (2018)
  • Author(s): Arae Ken、Morita Hideaki、Unno Hirotoshi、Motomura Kenichiro、Toyama Sumika、Okada Naoko、Ohno Tatsukuni、Tamari Masato、Orimo Keisuke、Mishima Yuko、Suto Hajime、Okumura Ko、Sudo Katsuko、Miyazawa Hiroshi、Taguchi Haruhiko、Saito Hirohisa、Matsumoto Kenji、Nakae Susumu
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 11721-11721
  • DOI: 10.1038/s41598-018-30259-2
  • Peer Reviewed / Open Access
• [Journal Article] IL-33 induces functional CCR7 expression in human mast cells. (2018)
  • Author(s): Emi-Sugie M, Toyama S, Matsuda A, Saito H, Matsumoto K.
  • Journal Title: J Allergy Clin Immunol. Volume: 142(4) Issue: 4 Pages: 1341-1344
  • DOI: 10.1016/j.jaci.2018.06.007
  • Peer Reviewed / Open Access
• [Journal Article] IL-33 induces functional CCR7 expression in human mast cells. (2018)
  • Author(s): 1.Emi-Sugie, M., Toyama, S. Matsuda, A. Saito, H. and Matsumoto, K.
  • Journal Title: J Allergy Clin Immunol. Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] Human eosinophils constitutively express a unique serine protease, PRSS33. (2017)
  • Author(s): 1.Toyama, S., Okada, N., Matsuda, A., Morita, H., Saito, H., Fujisawa, T., Nakae, S., Karasuyama, H., and Matsumoto, K.
  • Journal Title: Allergol Int. Volume: 66 Pages: 463-471
  • NAID: 130005858869
  • Peer Reviewed / Open Access
• [Presentation] Possible role for CD26/DPPIV in regulating mechanical itch (Alloknesis). (2019)
  • Author(s): Eriko Komiya-Suyama, Ryo Hatano, Takumi Itoh, Haruna Otsuka, Yayoi Kamata, Kotaro Honda, Sumika Toyama, Catharina Sagita Moniaga, Kei Ohnuma, Mitsutoshi Tominaga, Chikao Morimoto, Kenji Takamori.
  • Organizer: 28th EADV Congress.
  • Int'l Joint Research
• [Presentation] Elucidation of the signaling pathway involved in Sema3A gene expression in normal human epidermal keratinocytes. (2019)
  • Author(s): Yayoi kamata, Mitsutoshi Tominaga, Yoshie Umehara, Kotaro Honda, Atsuko Kamo, Sumika Toyama, Yasushi Suga, Kenji Takamori.
  • Organizer: 28th EADV Congress.
  • Int'l Joint Research
• [Presentation] Possible roles of eosinophil-sensory nerve communication in atopic dermatitis. (2019)
  • Author(s): Sumika Toyama, Reiko Sato-Fukami, Hideoki Ogawa, Yasushi Suga, Mitsutoshi Tominaga, Kenji Takamori.
  • Organizer: 118回 日本皮膚科学会総会
• [Presentation] 加齢皮膚におけるアロネーシスの発症メカニズムの解明と治療法の開発 (2019)
  • Author(s): 冨永光俊、古宮栄利子、本田耕太郎、外山扇雅、鎌田弥生、髙森建二
  • Organizer: 第15回加齢皮膚医学研究会
• [Presentation] 加齢皮膚で誘発される機械的かゆみ調節機構の解明 (2019)
  • Author(s): 古宮栄利子、冨永光俊、波多野良、伊藤匠、大塚春奈、本田耕太郎、外山扇雅、鎌田弥生、大沼圭、森本幾夫、髙森建二
  • Organizer: 第15回加齢皮膚医学研究会
• [Presentation] Regulatory T cells modulate skin inflammation in atopic dermatitis model mouse. (2017)
  • Author(s): 1.Sumika Toyama, Hironori Matsuda, Ryohei Kosaka, Hideoki Ogawa, Mitsutoshi Tominaga, Kenji Takamori.
  • Organizer: The 42nd Annual meeting of the Japanese Society for Investigative Dermatology.