Staphylococcus aureus toxin contributes to the development of food allergy after epicutaneous sensitization?

• Project/Area Number: 19K17895
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Juntendo University
• Principal Investigator: Uchida Shino 順天堂大学, 医学部, 非常勤助教 (30838438)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 食物アレルギー / 経皮感作 / 黄色ブドウ球菌毒素 / マスト細胞 / 黄色ぶどう球菌

Outline of Research at the Start

アトピー性皮膚炎は、食物アレルギーの発症に相関すること、黄色ブドウ球菌毒素のδ-toxin がアトピー性皮膚炎を増悪させることに着目し、δ-toxinが経皮感作を増強して食物アレルギーを強く誘導するという仮説を立て、そのメカニズムを解明することである。
卵白アルブミン・δ-toxinによる経皮感作を行い、食物アレルギーを誘導し、解析を行う。
またδ-toxin受容体を同定して経皮感作のメカニズムを解明し、新規治療法開発の分子基盤を形成する。

Outline of Final Research Achievements

We used murine models of food allergy following epicutaneous sensitization and demonstrated that Staphylococcus aureus-derived delta-toxin in skin promoted epicutaneous sensitization to food allergen and food allergic responses after the intake of food allergen. Our results suggested that delta-toxin in the skin caused the release of several cytokines from keratinocytes, one of which strongly induced the translocation of food allergen-loaded dendric cells to the draining lymph node and the production of food allergen-specific IgE, resulting in intestinal mast cell degranulation-mediated food allergic responses following the intake of food allergen.

Academic Significance and Societal Importance of the Research Achievements

本研究により、アトピー性皮膚炎患者の皮膚に多い黄色ブドウ球菌毒素のデルタトキシンが経皮感作とそれに付随する食物アレルギーの発症を強く促進することが病態メカニズムとともに明らかになった。これらの研究成果は、増加の一途をたどる国民病である食物アレルギーの病態解明とともに病態に基づく予防・治療法の開発につながる可能性があり、学術的意義と社会的意義有すると考えられる。

Research Products

• [Int'l Joint Research] University Hospital Erlangen/Medical Faculty Carl Gustav(ドイツ)
• [Journal Article] CD300f分子とアレルギー (2021)
  • Author(s): 貝谷綾子、伊沢久未、内田志野、亀井杏菜、前原明絵、安藤智暁、北浦次郎
  • Journal Title: 科学評論社、臨床免疫・アレルギー科 Volume: 75 Pages: 218-225
  • NAID: 40022478993
• [Journal Article] CD300fは食物アレルギーの治療標的となりうる (2020)
  • Author(s): 内田志野、伊沢久未、安藤智暁、貝谷綾子、北浦次郎
  • Journal Title: 科学評論社、臨床免疫・アレルギー科 Volume: 74 Pages: 398-405
• [Journal Article] Differential lipid recognition by mouse versus human CD300f, inhibiting passive cutaneous anaphylaxis, depends on a single amino acid substitution in its immunoglobulin-like domain (2020)
  • Author(s): Izawa K, Kaitani A, Ando T, Maehara A, Nagamine M, Yamada H, Ando T, Ide T, Matsuzawa M, Okamoto Y, Yin E, Fukase S, Wang H, Kamei A, Uchida S, Keiko M, Nakano N, Uchida K, Tamura N, Ikeda K, Ebihara N, Shimizu T, Voehringer D, Roers A, Ogawa H, Okumura K, Kitaura J
  • Journal Title: J Invest Dermatol Volume: 140 Pages: 710-713
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CD300f is a potential therapeutic target for the treatment of food allergy (2019)
  • Author(s): Uchida Shino、Izawa Kumi、Ando Tomoaki、Yamada Hiromichi、Uchida Koichiro、Negishi Naoko、Kaitani Ayako、Maehara Akie、Nagamine Masakazu、Kamei Anna、Takamori Ayako、Maeda Keiko、Nakano Nobuhiro、Shimizu Toshiaki、Ogawa Hideoki、Okumura Ko、Nagahara Akihito、Watanabe Sumio、Kitaura Jiro
  • Journal Title: Allergy Volume: 75 Issue: 2 Pages: 471-474
  • DOI: 10.1111/all.14034
  • NAID: 40022209298
  • Peer Reviewed / Open Access
• [Presentation] Staphylococcus aureus d-toxin in skin promotes the development of food allergy following epicutaneous sensitization. (2021)
  • Author(s): Anna Kamei, Hiromichi Yamada, Kumi Izawa, Tomoaki Ando, Ayako Kaitani, Akie Maehara, Hexing Wang, Koji Tokushige, Shino Uchida, Nobuhiro Nakano, Ko Okumura, Jiro Kitaura
  • Organizer: 第50回日本免疫学会学術集会
• [Presentation] An inhibitory receptor CD300f inhibits the pathogenesis of OVA-induced food allergy in mice (2019)
  • Author(s): Anna Kamei, Shino Uchida, Hiromichi Yamada, Kumi Izawa, Tomoaki Ando, Naoko Negishi, Akie Maehara, Ayako Kaitani, Yoko Okamoto, Nobuhiro Nakano, Ko Okumura, Jiro Kitaura
  • Organizer: 第48回日本免疫学会