Onset mechanisms of atopic dermatitis induced by saturate fatty acid of breast milk

• Project/Area Number: 26500010
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Integrated Nutrition Science
• Research Institution: Hiroshima University
• Principal Investigator: Kanno Masamoto 広島大学, 医歯薬保健学研究院(医), 教授 (40161393)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アレルギー疾患 / アトピー性皮膚炎 / 母乳 / 自然免疫系 / 自然リンパ球 / メタボローム解析 / マウス発症モデル / モデルマウス / 脂肪酸 / アレルギー / サイトカイン / IgE / インフラマソーム / 自然免疫 / マウスモデル

Outline of Final Research Achievements

Breastfeeding is believed to influence the infants’ immune system development and may even affect various immunological responses later in life. A cohort study was carried out to monitor atopic dermatitis(AD) development in breast-fed children. About 10% of the AD+ mothers milk was positive (DAMPs+) when introduced to human cells in vitro. To identify the DAMP molecules, targeted metabolomics analysis was performed. This indicated presence of higher amount of several saturated fatty acids (SFA). In vivo study of HR-1 hairless mice breast-fed on lactating period with high SFA diet showed a higher incidence of skin eczema and AD-like skin symptoms. We are focusing on innate immunity and how SFA promote skin eczema and IgE increase. Among the changes observed in high SFA-milk diet mice include alterations in the intestinal and skin lymphocytes development. We concluded immunological mechanisms and aspect of nutrition based development mechanisms of atopic dermatitis.

Research Products

• [Int'l Joint Research] Birmingham Univ/Oxford Univ. Jesus college(英国)
• [Int'l Joint Research] Centre d'Immunologie de Marseille-Luminy(フランス)
• [Int'l Joint Research] Birmingham大学(英国)
• [Journal Article] Identification of DAMPs molecules in mother’s milk of a cohort study on atopic dermatitis in breastfed infants: Mouse model study and correlation with gut ILCs (2016)
  • Author(s): KANNO, M., Kong, W.-S., Inoue, H., Shimojyo, N., Tsuyama, N., Arita, M., Guo, Y.
  • Journal Title: EUROPEAN J. IMMUNOL. Volume: 46 Issue: S1 Pages: 1-1274
  • DOI: 10.1002/eji.201670200
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Epstein-Barr virus-related MTX-LPD in rheumatoid arthritis patients exhibits a viral pattern of the CD64 and CD35 expression on neutrophils: three case reports. (2015)
  • Author(s): Mokuda S, Miyazaki T, Saeki Y, Masumoto J, Kanno M, Takasugi K.
  • Journal Title: Modern rheumatology Volume: 25 Issue: 1 Pages: 166-168
  • DOI: 10.3109/14397595.2013.875641
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The proto-oncogene survivin splice variant 2B is induced by PDGF and leads to cell proliferation in rheumatoid arthritis fibroblast-like synoviocytes. (2015)
  • Author(s): Mokuda S, Miyazaki T, Ito Y, Yamasaki S, Inoue H, Guo Y, Kong WS, Kanno M, Takasugi K, Sugiyama E, Masumoto J.
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 9795-9795
  • DOI: 10.1038/srep09795
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] CD1a+ survivin+ dendritic cell infiltration in dermal lesions of systemic sclerosis. (2015)
  • Author(s): Mokuda S, Miyazaki T, Ubara Y, Kanno M, Sugiyama E, Takasugi K, Masumoto J.
  • Journal Title: Arthritis Res Ther. Volume: 17 Issue: 1 Pages: 275-275
  • DOI: 10.1186/s13075-015-0785-0
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] A role of the Ubiquitin-modifying enzyme A20 in regulatory T cells. (2017)
  • Author(s): Yun Guo, Fuqiang Chen, Weng-Sheng Kong, Hiroaki Honda and Masamoto Kanno
  • Organizer: International KTCC (Kyoto T Cell Conference)
  • Place of Presentation: Kyoto JAPAN
  • Year and Date: 2017-03-13
  • Int'l Joint Research
• [Presentation] Identification of DAMPs molecules in mothers’ milk of a cohort study on atopic dermatitis in breastfed infants: Mouse model and correlation with gut/skin ILCs. (2017)
  • Author(s): Masamoto Kanno, Weng-Sheng Kong, Yun Gul, Fuqiang Chen, Zhichao Cao, Naoki Shimojo, Tsutomu Masujima, Naohiro Tsuyama and Hiroko Inoue
  • Organizer: International KTCC (Kyoto T Cell Conference)
  • Place of Presentation: Kyoto JAPAN
  • Year and Date: 2017-03-13
  • Int'l Joint Research
• [Presentation] Molecular mechanisms of Low-dose radiation effects on Hematopietic stem cell (2017)
  • Author(s): Y.Ohono, K.Suzuki, M.yamafuji, Y.Guo, M.kanno, N.Shirasu, K.Naka, S.Yasunaga and Y.Takihara
  • Organizer: Molecular mechanisms of Low-dose radiation effects on Hematopietic stem cell
  • Place of Presentation: Hiroshima JAPAN
  • Year and Date: 2017-02-21
  • Int'l Joint Research
• [Presentation] Involvement of ILCs in the pathogenesis of atopic dermatitis mouse model. (2016)
  • Author(s): Kong, W.-S., Inoue, H., Shimojyo, N., Tsuyama, N., Arita, M., Guo, Y.and KANNO, M.,
  • Organizer: 第４５回日本免疫学会学術集会
  • Place of Presentation: Okinawa convention Center 宜野湾市 沖縄
  • Year and Date: 2016-12-05
• [Presentation] A role of the Ubiquitin-modifying enzyme A20 in regulatory T cells. (2016)
  • Author(s): Yun Guo, Fuqiang Chen, Weng-Sheng Kong, Hiroaki Honda and Masamoto Kanno
  • Organizer: 第４５回日本免疫学会学術集会
  • Place of Presentation: Okinawa convention Center 宜野湾市 沖縄
  • Year and Date: 2016-12-05
• [Presentation] 造血幹細胞の低線量被曝に対する分子応答の解析 (2016)
  • Author(s): 大野芳典、鈴木―竹立恭子、山藤幹茂子、郭芸、菅野雅元、白須直人、大坪素秋、仲一仁、安永晋一郎、瀧原義宏
  • Organizer: 第３９回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜 横浜市
  • Year and Date: 2016-11-30
• [Presentation] Identification of DAMPs molecules in mother’s milk of a cohort study on atopic dermatitis in breastfed infants: Mouse model study and correlation with gut ILCs. (2016)
  • Author(s): KANNO, M., Kong, W.-S., Inoue, H., Shimojyo, N., Tsuyama, N., Arita, M., Guo, Y.
  • Organizer: Internationa Congress of Immunology (ICI2016)
  • Place of Presentation: Melbourne Australia
  • Year and Date: 2016-08-20
  • Int'l Joint Research / Invited
• [Presentation] アトピー性皮膚炎・出生コホート解析：母乳中DAMPs活性物質の同定、免疫学的作用機序の検討 (2016)
  • Author(s): 菅野雅元、Kong Weng-Sheng、津山尚宏、有田 誠、升島;努、郭 芸、下条直樹、井上洋子
  • Organizer: 第６５回日本アレルギー学会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2016-06-17
  • Invited
• [Presentation] Detection of suppressive activity on innate immune DAMPs response in sepsis (2016)
  • Author(s): Ho Minh Van, Nobuyuki Hirohashi, Kong Weng Sheng, Masamoto Kanno,3,4, Koichi Tanigawa1,5, Nobuaki Shime1
  • Organizer: The 5th International Symposium: Revitalization Strategies After Radiation Disaster
  • Place of Presentation: Hiroshima Japan
  • Year and Date: 2016-02-13
  • Int'l Joint Research
• [Presentation] アレルギー発症・出征コホートによる、母乳中DAMPs活性原因物質の同定。 (2015)
  • Author(s): 菅野雅元、Weng-sheng Kong, 津山尚宏、下条直樹、、郭芸、井上洋子。
  • Organizer: BMB２０１５（第３８回日本分子生物学会年会＋第８８回日本生化学会大会）
  • Place of Presentation: 神戸ポートアイランド 神戸
  • Year and Date: 2015-12-01
• [Presentation] Identification of DAMPs in mother’s milk of a cohort study on atopic dermatitis in breastfed infants ; part 1: In vivo study of skin and gut of breastfed HR-1 mice (2015)
  • Author(s): KONG Weng Sheng, INOUE Hiroko, GUO Yun, SHIMOJO Naoki, KANNO Masamoto
  • Organizer: 第４４回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（札幌）
  • Year and Date: 2015-11-18
• [Presentation] Identification of DAMPs in mother’s milk of a cohort study on atopic dermatitis in breastfed infants; part 2: In vitro analysis of mechanisms of NLRP3 inflammasome activation by saturated fatty acids (2015)
  • Author(s): INOUE Hiroko. KONG Weng Sheng, GUO Yun, SHIMOJO Naoki, KANNO Masamoto
  • Organizer: 第４４回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（札幌）
  • Year and Date: 2015-11-18
• [Presentation] Detection of immune suppressive activity in septic serum in the presence of DAMPs signal (2015)
  • Author(s): Ho Minh Van, Kong weng sheng, Hirohashi Nobuyuki, Masamoto Kanno
  • Organizer: 第４４回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（札幌）
  • Year and Date: 2015-11-18
• [Presentation] A role of Ubiqiti-modifying enzyme A20 in regulatory T cell (2015)
  • Author(s): Guo Yun, Mokuda Shou, Kong wheng sheng, Kanno Masamoto
  • Organizer: 第４４回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（札幌）
  • Year and Date: 2015-11-18
• [Presentation] The proto-oncogene survivin splice variant 2B leads to cell proliferation in rheumatoid arthritis fibroblast-like synoviocytes (2015)
  • Author(s): Sho Mokuda, Miyazaki Tatsuhiko, Satoshi Yamasaki, Junya Masumoto, Kong Weng Sheng, Yun Guo, Hiroko Inoue, Masamoto Kanno
  • Organizer: 第４４回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（札幌）
  • Year and Date: 2015-11-18
• [Presentation] アレルギー発症・出生コホートによる、アトピー性皮膚炎発症と母乳中DAMPs活性原因物質の同定。 (2015)
  • Author(s): 菅野雅元、Weng-sheng Kong, 津山尚宏、下条直樹、河野陽一、郭芸、井上洋子。
  • Organizer: 第６４回日本アレルギー学会学術大会
  • Place of Presentation: グランドプリンスホテル新高輪、東京
  • Year and Date: 2015-05-26
• [Remarks] 免疫学研究室HP
  • URL: https://www.hiroshima-u.ac.jp/med/research/lab/basis/Immunology