Epithelial–immune microenvironment (EIME) in acne

• Project/Area Number: 21K08303
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kagawa University
• Principal Investigator: Dainichi Teruki 香川大学, 医学部, 教授 (20423543)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ざ瘡

Outline of Research at the Start

ざ瘡は毛包漏斗部と脂腺開口部の角化異常と脂腺の活性化を伴う「毛包炎」で、Cutibacterium acnes の増殖は必ずしも感染症とはみなされず、自己炎症性疾患の一所見としても生じる。好中球の遊走とTヘルパー (TH) 17型リンパ球の活性化がみられ、脂質代謝や酸化ストレスとの関連も知られる。毛包の免疫恒常性、代謝と免疫の相互制御の観点での理解は必ずしも進んでいない。申請者は、ざ瘡が、TH17型炎症、角化異常、脂質・酸化ストレス異常の３点で乾癬に似ている可能性に着目した。本研究ではざ瘡の発症における上皮-免疫細胞間の「炎症の回路」を明らかにし、新規治療の創出や予防に結びつける。

Outline of Final Research Achievements

This study addresses the epithelial-immune cell circuit in the pathogenesis of acne, leading to the creation of novel therapies and prevention. To evaluate the pathology of the follicular sebaceous gland system in experimental animals, first, Rhino mice were introduced from The Jackson Laboratory, USA, and transcriptome analysis was performed during the course of chemical peeling. Second, an acne animal model system was established using B6 mice by continuous topical application of fatty acids, and the suppression of the development of the disease by candidate low-molecular-weight compounds was evaluated.

Academic Significance and Societal Importance of the Research Achievements

ざ瘡は患者数でも経済規模でも人類最大の皮膚疾患でありながら、治療面において、1982年に発見されたイソトレチノインによるざ瘡の抑制作用に匹敵する進歩は40年以上みられない。とくに本邦ではざ瘡の基礎研究にかかわる研究者はごく限られる。本研究は、ざ瘡という疾患において、研究面で今後、アトピー性皮膚炎や乾癬の領域に匹敵する発展をリードしうる、先進的な取り組みとして位置づけることができる。

Research Products

• [Journal Article] C10orf99/GPR15L Regulates Proinflammatory Response of Keratinocytes and Barrier Formation of the Skin (2022)
  • Author(s): Dainichi Teruki、Nakano Yuri、Doi Hiromi、Nakamizo Satoshi、Nakajima Saeko、Matsumoto Reiko、Farkas Thomas、Wong Pui Mun、Narang Vipin、Moreno Traspas Ricardo、Kawakami Eiryo、Guttman-Yassky Emma、Dreesen Oliver、Litman Thomas、Reversade Bruno、Kabashima Kenji
  • Journal Title: Frontiers in Immunology Volume: 13 Pages: 825032-825032
  • DOI: 10.3389/fimmu.2022.825032
  • NAID: 120007192998
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Interferon-gamma induced APOBEC3B contributes to Merkel cell polyomavirus genome mutagenesis in Merkel cell carcinoma (2021)
  • Author(s): Que L, Li Y, Dainichi T, Kukimoto I, Nishiyama T, Nakano Y, Shima K, Suzuki T, Sato Y, Horike S, Aizaki H, Watashi K, Kato T, Aly HH, Watanabe N, Kabashima K, Wakae K, Muramatsu M.
  • Journal Title: J Invest Dermatol Volume: S0022-202X(21) Issue: 7 Pages: 02636-1
  • DOI: 10.1016/j.jid.2021.12.019
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Editorial: Regulation of Immunity by Non-Immune Cells. (2021)
  • Author(s): Dainichi T, Kabashima K, Ivanov II, Goto Y.
  • Journal Title: Front Immunol Volume: 12 Pages: 770847-770847
  • DOI: 10.3389/fimmu.2021.770847
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cutaneous Liver X Receptor Activation Prevents the Formation of Imiquimod-Induced Psoriatic Dermatitis. (2021)
  • Author(s): Otsuka M., Egawa G., Dainichi T., Okuno T., Ishida Y., Chow Z., Asahina R., Miyake T., Nomura T., Kitoh A., Yokomizo T., Kabashima K.
  • Journal Title: Journal of Investigative Dermatology Volume: 142(4) Issue: 4 Pages: 1233-1237.e1
  • DOI: 10.1016/j.jid.2021.08.432
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A ubiquitin-like protein encoded by the “noncoding” RNA TINCR promotes keratinocyte proliferation and wound healing (2021)
  • Author(s): Nita Akihiro、Matsumoto Akinobu、Tang Ronghao、Shiraishi Chisa、Ichihara Kazuya、Saito Daisuke、Suyama Mikita、Yasuda Tomoharu、Tsuji Gaku、Furue Masutaka、Katayama Bumpei、Ozawa Toshiyuki、Murata Teruasa、Dainichi Teruki、Kabashima Kenji、Hatano Atsushi、Matsumoto Masaki、Nakayama Keiichi I.
  • Journal Title: PLOS Genetics Volume: 17 Issue: 8 Pages: 1009686-1009686
  • DOI: 10.1371/journal.pgen.1009686
  • Peer Reviewed / Open Access
• [Journal Article] Anti‐BP230‐type papular non‐bullous pemphigoid with granular immunoglobulin G deposition at the papillary dermis (2021)
  • Author(s): Dainichi Teruki、Kaku Yo、Izumi Maiko、Kataoka Koki、Morishita Yoshiko、Koga Hiroshi、Ishii Norito
  • Journal Title: The Journal of Dermatology Volume: 48 Issue: 10
  • DOI: 10.1111/1346-8138.16070
  • Peer Reviewed
• [Journal Article] Dipeptidyl peptidase 4 inhibitor‐associated mucous membrane pemphigoid (2021)
  • Author(s): Suezawa Mei、Dainichi Teruki、Kaku Yo、Izumi Maiko、Kataoka Koki、Ishii Norito、Koga Hiroshi、Izumi Kentaro、Nishie Wataru
  • Journal Title: The Journal of Dermatology Volume: 48 Issue: 10 Pages: 1584-1587
  • DOI: 10.1111/1346-8138.16061
  • Peer Reviewed
• [Journal Article] Erythema punctatum Higuchi: reconsidering its relationship with adrenergic urticaria and eruptive pseudoangiomatosis (2021)
  • Author(s): Mori A.、Kaku Y.、Dainichi T.
  • Journal Title: Journal of the European Academy of Dermatology and Venereology Volume: 35 Issue: 11
  • DOI: 10.1111/jdv.17474
  • Peer Reviewed
• [Journal Article] Prolonged high-intensity exercise induces fluctuating immune responses to herpes simplex virus infection via glucocorticoids (2021)
  • Author(s): Adachi, A., Honda, T., Dainichi, T., Egawa, G., Yamamoto, Y., Nomura, T., Nakajima, S., Otsuka, A., Maekawa, M., Mano, N., Koyanagi, N., Kawaguchi, Y., Ohteki, T., Nagasawa, T., Ikuta, K., Kitoh, A., and Kabashima, K.
  • Journal Title: J. Allergy Clin. Immunol. Volume: 148 Issue: 6 Pages: 1575-1588.e7
  • DOI: 10.1016/j.jaci.2021.04.028
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Successful treatment of severe blepharitis in a patient with atopic dermatitis by topical delgocitinib (2021)
  • Author(s): Dainichi T.、Kaku Y.、Izumi M.、Kataoka K.
  • Journal Title: Clinical and Experimental Dermatology Volume: 46 Issue: 6 Pages: 1119-1120
  • DOI: 10.1111/ced.14651
  • Peer Reviewed
• [Journal Article] Pituitary adenylate cyclase-activating polypeptide promotes cutaneous dendritic cell functions in contact hypersensitivity. (2021)
  • Author(s): Yasuo Yamamoto 1, Atsushi Otsuka 2, Yoshihiro Ishida 3, Lai San Wong 4, Judith A Seidel 3, Yumi Nonomura 3, Chisa Nakashima 3, Saeko Nakajima 3, Akihiko Kitoh 3, Takashi Nomura 3, Teruki Dainichi 3, Tetsuya Honda 3, Wataru Amano 1, Noriko Konishi 5, Mikio Hayashi 5, Mutsuyoshi Matsushita 5, Kenji Kabashima 6
  • Journal Title: J Allergy Clin Immunol. Volume: 18;S0091-6749(21) Issue: 3 Pages: 00218-9
  • DOI: 10.1016/j.jaci.2021.02.005
  • Peer Reviewed
• [Journal Article] Temporal triangular alopecia confined to the frontal scalp. (2021)
  • Author(s): Tahara J, Dainichi T, Kaku Y, Kataoka T, Kishimoto H, Kogame T, Kabashima K.
  • Journal Title: J Dermatol Volume: 48 Issue: 4
  • DOI: 10.1111/1346-8138.15776
  • Peer Reviewed / Open Access
• [Journal Article] PD-L1 on mast cells suppresses effector CD8+ T-cell activation in the skin in murine contact hypersensitivity (2021)
  • Author(s): Hirano Tomoko、Honda Tetsuya、Kanameishi Shuto、Honda Yuki、Egawa Gyohei、Kitoh Akihiko、Nakajima Saeko、Otsuka Atsushi、Nomura Takashi、Dainichi Teruki、Yaguchi Tomonori、Inozume Takashi、Kataoka Tatsuki R.、Tamada Koji、Kabashima Kenji
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: in press Issue: 2 Pages: 00178-00178
  • DOI: 10.1016/j.jaci.2020.12.654
  • Peer Reviewed / Open Access / Int'l Joint Research