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Differentiation and function of Foxp3-negative IL-10-producing regulatory T cells on mucosal bacterial infection

Research Project

Project/Area Number 26293400
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Nagai Shigenori  東京医科歯科大学, 医歯(薬)学総合研究科, 准教授 (50348801)

Co-Investigator(Kenkyū-buntansha) 東 みゆき  東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (90255654)
Co-Investigator(Renkei-kenkyūsha) YOSHIMURA Akihiko  慶應義塾大学, 医学部, 教授 (90182815)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
KeywordsIL-10 / ヘルパーT細胞 / PI3K / 免疫学 / 細菌感染 / 粘膜免疫
Outline of Final Research Achievements

Since Foxp3-negative, IL-10-producing regulatory T (Tr1) cells are quite important for the suppression of chronic inflammation, I tried to investigate the regulatory mechanisms of Tr1 differentiation. When I added the inhibitor of PI3K, a kind of lipid kinases, in Tr1 differentiation by IL-27, I was able to suppress Tr1 differentiation. In contrast, Tr1 differentiation was enhanced when the PI3K pathway was augmented. These results suggest that PI3K pathway positively regulates the differentiation of IL-27-induced Tr1 cells.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (26 results)

All 2016 2015 2014 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Acknowledgement Compliant: 1 results,  Open Access: 4 results) Presentation (18 results) (of which Int'l Joint Research: 3 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] TGF-β-induced phosphorylation of Akt and Foxo transcription factors negatively regulates induced regulatory T cell differentiation.2016

    • Author(s)
      Kurebayashi Y, Baba Y, Minowa A, Nadya NA, Azuma M, Yoshimura A, Koyasu S, Nagai S.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 480 Issue: 1 Pages: 114-119

    • DOI

      10.1016/j.bbrc.2016.09.153

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Delayed Propionibacterium acnes surgical site infections occur only in the presence of an implant2016

    • Author(s)
      Y. Shiono, K. Ishii, S. Nagai, H. Kakinuma, A. Sasaki, H. Funao, T. Kuramoto1, K. Yoshioka, H. Ishihama, N. Isogai, K. Takeshima, T. Tsuji, Y. Okada, S. Koyasu, M. Nakamura, Yoshiaki Toyama, M. Aizawa, and M. Matsumoto
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 32758-32758

    • DOI

      10.1038/srep32758

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The RNA Binding Protein Mex-3B Is Required for IL-33 Induction in the Development of Allergic Airway Inflammation.2016

    • Author(s)
      Yamazumi Y, Sasaki O, Imamura M, Oda T, Ohno Y, Shiozaki-Sato Y, Nagai S, Suyama S, Kamoshida Y, Funato K, Yasui T, Kikutani H, Yamamoto K, Dohi M, Koyasu S, Akiyama T.
    • Journal Title

      Cell Rep.

      Volume: 16 Issue: 9 Pages: 2456-2471

    • DOI

      10.1016/j.celrep.2016.07.062

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel hydroxyapatite film coated with ionic silver via inositol hexaphosphate chelation prevents implant-associated infection.2016

    • Author(s)
      Funao H, Nagai S, Sasaki A, Hoshikawa T, Tsuji T, Okada Y, Koyasu S, Toyama Y, Nakamura M, Aizawa M, Matsumoto M, Ishii K.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 23238-23238

    • DOI

      10.1038/srep23238

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel mouse model of soft-tissue infection using bioluminescence imaging allows noninvasive, real-time monitoring of bacterial growth.2014

    • Author(s)
      Yoshioka K, Ishii K, Kuramoto T, Nagai S, Funao H, Ishihama H, Shiono Y, Sasaki A, Aizawa M, Okada Y, Koyasu S, Toyama Y, Matsumoto M
    • Journal Title

      PLoS One

      Volume: 9 Issue: 9 Pages: e106367-e106367

    • DOI

      10.1371/journal.pone.0106367

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] CELLULAR RESPONSES OF IMMUNE CELLS TO GLASS CERAMICS IN THE CaO-P2O5-SiO2-B2O3 SYSTEM.2016

    • Author(s)
      Rihoko Kizukuri, Kiyotaka Yamada, Michiyo Honda, Shigenori Nagai and Mamoru Aizawa.
    • Organizer
      16th Australasian BioCeramics Symposium.
    • Place of Presentation
      Brisbane, Australia.
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of IL-10 production from IL-27-induced Tr1 cells by PI3K-Akt pathway.2016

    • Author(s)
      Adiba Nadya Niken, Miyuki Azuma, Shigenori Nagai
    • Organizer
      第45回日本免疫学会総会・学術集会
    • Place of Presentation
      沖縄コンベンションセンター 沖縄県宜野湾市
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Features of oral mucosal inflammation -comparative studies with skin inflammation-.2016

    • Author(s)
      Worawalun Hirunwidchayarat, Tatsukuni Ohno, Siwen Kang, Shigenori Nagai, Michio Tomura, Miyuki Azuma
    • Organizer
      第45回日本免疫学会総会・学術集会
    • Place of Presentation
      沖縄コンベンションセンター 沖縄県宜野湾市
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Tr1分化におけるPI3Kの役割.2016

    • Author(s)
      Niken Adiba Nadya, 東 みゆき,永井 重徳
    • Organizer
      第58回歯科基礎医学会学術大会
    • Place of Presentation
      札幌コンベンションセンター 北海道札幌市
    • Year and Date
      2016-08-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 口腔粘膜炎症において局所に集積するT細胞の解析.2016

    • Author(s)
      Hirunwidchayarat Worawalun,大野 建州,Kang Siwen,永井 重徳,東 みゆき
    • Organizer
      第58回歯科基礎医学会学術大会
    • Place of Presentation
      札幌コンベンションセンター 北海道札幌市
    • Year and Date
      2016-08-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] Phosphorylation of Akt and Foxos induced by TGF-β negatively regulates the differentiation of induced regulatory T cells.2016

    • Author(s)
      Shigenori Nagai, Yutaka Kurebayashi, Yukiko Baba, Akiko Minowa, Miyuki Azuma, Akihiko Yoshimura, Shigeo Koyasu.
    • Organizer
      16th International Congress of Immunology
    • Place of Presentation
      Melbourne, Australia.
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CaO-P2O5-SiO2-B2O3系ガラスセラミックスの免疫細胞応答性.2016

    • Author(s)
      木造理萌子,山田清貴,本田みちよ,永井重徳,相澤守.
    • Organizer
      無機マテリアル学会第132回講演会.
    • Place of Presentation
      船橋市民文化創造館 千葉県船橋市
    • Year and Date
      2016-06-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] Role of PI3K in Tr1 cell differentiation.2015

    • Author(s)
      Adiba Nadya Niken, Miyuki Azuma, Shigenori Nagai
    • Organizer
      第44回日本免疫学会総会・学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Masticatory mucosa-associated B7-H1 limits mucosal tissue damage.2015

    • Author(s)
      Siwen Kang, Tatsukuni Ohno, Shigenori Nagai, Miyuki Azuma
    • Organizer
      第44回日本免疫学会総会・学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Recruiting T cells to the oral mucosa under the inflammatory condition.2015

    • Author(s)
      Worawalun Hirunwidchayarat, Tatsukuni Ohno, Siwen Kang, Shigenori Nagai, Miyuki Azuma
    • Organizer
      第44回日本免疫学会総会・学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Morphological Observation of Immune Cells Derived from Mouse Spleen to Hydroxyapatite Ceramics Surface-Modified with Inositol Phosphate.2015

    • Author(s)
      Kiyotaka Yamada, Mariko Nakamura, Shigenori Nagai, Michiyo Honda, Mamoru Aizawa
    • Organizer
      Bioceramics 27th Symphosium and Annual Meeting of the International Society for Ceramics in Medicine
    • Place of Presentation
      Bali, Indonesia.
    • Year and Date
      2015-10-27
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 合成樹脂製インプラントにおける新規抗菌加工の安全性評価―細胞毒性とバイオメカニクス的検討―.2015

    • Author(s)
      石濱 寛子, 石井 賢, 柿沼 祐亮, 塩野 雄太, 蔵本 哲也, 吉岡 研之, 船尾 陽生, 永井 重徳, 佐々木 文, 相澤 守, 岡田 保典, 小安 重夫, 松本 守雄, 中村 雅也
    • Organizer
      第30回日本整形外科学会基礎学術集会
    • Place of Presentation
      富山国際会議場(富山県富山市)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] 合成樹脂製インプラントにおける新規抗菌開発法の開発.2015

    • Author(s)
      石濱 寛子, 石井 賢, 柿沼 祐亮, 塩野 雄太, 蔵本 哲也, 吉岡 研之, 船尾 陽生, 永井 重徳, 佐々木 文, 相澤 守, 岡田 保典, 小安 重夫, 松本 守雄, 中村 雅也
    • Organizer
      第30回日本整形外科学会基礎学術集会
    • Place of Presentation
      富山国際会議場(富山県富山市)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] イノシトールリン酸を表面修飾した水酸アパタイトセラミックスに対するマウス脾臓由来免疫細胞の応答性.2015

    • Author(s)
      山田 清貴,中村 まり子,永井 重徳,本田 みちよ,相澤 守
    • Organizer
      セラミックス協会第28回秋季シンポジウム
    • Place of Presentation
      富山大学(富山県富山市)
    • Year and Date
      2015-09-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] Phosphorylation of Akt and Foxos induced by TGF-β negatively controls the differentiation of Induced Regulatory T Cells.2014

    • Author(s)
      Shigenori Nagai, Yutaka Kurebayashi, Miyuki Azuma, Akihiro Yoshimura, Shigeo Koyasu
    • Organizer
      第43回日本免疫学会総会・学術集会
    • Place of Presentation
      京都
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] TGF-βによるAktおよびFoxoのリン酸化はiTreg分化を負に制御する2014

    • Author(s)
      永井 重徳,紅林 泰,東 みゆき,吉村 昭彦,小安 重夫.
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cellular Responses of Immune Cells Derived from Mouse Spleen to Hydroxyapatite Ceramics Surface-modified with Inositol Phosphate.2014

    • Author(s)
      Kiyotaka Yamada, Mariko Nakamura, Shigenori Nagai, Michiyo Honda, Mamoru Aizawa
    • Organizer
      26th Symphosium and Annual Meeting of the International Society for Ceramics in Medicine
    • Place of Presentation
      Barcelona, Italy.
    • Year and Date
      2014-11-06 – 2014-11-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] イノシトールリン酸を表面修飾した水酸アパタイトセラミックスに対するマウス脾臓由来免疫細胞の応答性.2014

    • Author(s)
      山田 清貴,中村 まり子,永井 重徳,本田 みちよ,相澤 守
    • Organizer
      第24回無機リン化学討論会
    • Place of Presentation
      高知
    • Year and Date
      2014-09-25 – 2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Book] アバス-リックマン-ピレ「分子細胞免疫学」第7版(第12章)2014

    • Author(s)
      白木 文子,永井 重徳.(監訳:松島 綱治,山田 幸宏)
    • Total Pages
      627
    • Publisher
      エルゼビア・ジャパン
    • Related Report
      2014 Annual Research Report
  • [Remarks] 東京医科歯科大学 分子免疫学分野

    • URL

      http://www.tmd.ac.jp/mim/

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report 2014 Annual Research Report
  • [Patent(Industrial Property Rights)] 細胞培養基材、細胞培養基材の製造方法、細胞培養方法、及び細胞培養装置2014

    • Inventor(s)
      相澤守,中村まり子,山田清貴,永井重徳
    • Industrial Property Rights Holder
      相澤守,中村まり子,山田清貴
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-09-22
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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