Analysis of mechanisms by which CX3CR1high myeloid cells regulate gut homeostais

• Project/Area Number: 23790536
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: KAYAMA Hisako 大阪大学, 医学(系)研究科(研究院), 助教 (40548814)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 腸管免疫 / 自然免疫 / 粘膜免疫 / IBD / 制御性細胞 / 自然免疫細胞

Research Abstract

We have identified that CX3CR1high CD11b+ CD11c+ myeloid cells (regulatory myeloid cells: Mreg cells) preferentially interacted with effector T cells via high expression of ICAM-1/VCAM, but did not activate effector T cells owing to the IL-10/Stat3-dependent suppression of CD80 and CD86 expression. In addition, our study showed that the severity of intestinal inflammation was improved by administration of wild-type Mreg cells in LysM-cre; Stat3flox/flox mice with Mreg cells lacking suppressive activity. These findings indicate the possibility that the impaired Mreg function is responsible for onset or/and progression of IBD.

Research Products

• [Journal Article] Insight into the flagella type III export revealed by the complex structure of the type III ATPase and its regulator. (2017)
  • Author(s): Imada, K., Minamino, T., Uchida, Y., Kinoshita, M., Namba, K.
  • Journal Title: PNAS Volume: 110 Issue: 13 Pages: 12271-12276
  • DOI: 10.1073/pnas
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ecto-nucleoside triphosphate diphosphohydrolase 7 controls Th17 cell responses through regulation of luminal ATP in the small intestine (2013)
  • Author(s): Kusu T, Kayama H, Kinoshita M, Jeon SG, Ueda Y, Goto Y, Okumura R, Saiga H, Kurakawa T, Ikeda K, Kunisawa J, Kiyono H, Okumura M, Yamamoto M, Takeda K.
  • Journal Title: J Immunol Volume: 190(2) Pages: 774-83
  • Peer Reviewed
• [Journal Article] CREBH determines the severity of sulpyrine-induced fatal shock. (2013)
  • Author(s): Kamiyama N, Yamamoto M, Saiga H, Ma JS, Ohshima J, Machimura S, Sasai M, Kimura T, Ueda Y, Kayama H, Takeda K.
  • Journal Title: . PLoS One Volume: 8(2)
  • Peer Reviewed
• [Journal Article] Regulation of intestinal homeostasis by innate and adaptive immunity (2012)
  • Author(s): Kayama H, Takeda K
  • Journal Title: Int Immunol Volume: 24(11) Pages: 673-80
  • Peer Reviewed
• [Journal Article] Dietary folic acid promotes survival of Foxp3+ regulatory T cells in the colon (2012)
  • Author(s): Kinoshita M, Kayama H, Kusu T, Yamaguchi T, Kunisawa J, Kiyono H, Sakaguchi S, Takeda K
  • Journal Title: J.Immunol Volume: 189(6) Pages: 2869-78
  • Peer Reviewed
• [Journal Article] Intestinal CX3C chemokine receptor 1high (CX3CR1high) myeloid cells prevent T-cell-dependent colitis (2012)
  • Author(s): Kayama H, Ueda Y, Sawa Y, Jeon SG, Ma JS, Okumura R, Kubo A, Ishii M, Okazaki T, Murakami M, Yamamoto M, Yagita H, Takeda K.
  • Journal Title: Proc Natl Acad Sci USA. Volume: in press
  • Peer Reviewed
• [Journal Article] Probiotic Bifidobacterium breve induces IL-10-producing Tr1 cells in the colon (2012)
  • Author(s): Jeon SG *, Kayama H *, Ueda Y, Takahashi T, Asahara T, Tsuji T, Tsuji M.N, Kiyono H, Ma JS Kusu T, Okumura R, Hara H, Yoshida H, Yamamoto M, Nomoto K, Takeda K
  • Journal Title: PLoS Pathogs Volume: in press
  • Peer Reviewed
• [Journal Article] The lactic acid bacterium Pediococcus acidilactici suppresses autoimmune encephalomyelitis by inducing IL-10-producing regulatory T cells (2011)
  • Author(s): Takata K, Kinoshita M, Okuno T, Moriya M, Kohda T, Honorat JA, Sugimoto T, Kumanogoh A, Kayama H, Takeda K, Sakoda S, Nakatsuji Y.
  • Journal Title: PLoS One Volume: 6 (11)
  • Peer Reviewed
• [Journal Article] ATF6beta is a host cellular target of the Toxoplasma gondii virulence factor ROP18 (2011)
  • Author(s): amamoto M, Ma JS, Mueller C, Kamiyama N, Saiga H, Kubo E, Kimura T, Okamoto T, Okuyama M, Kayama H, Nagamune K, Takashima S, Matsuura Y, Soldati-Favre D, Takeda K.
  • Journal Title: J.Exp.Med. Volume: 208 (7) Pages: 1533-46
  • Peer Reviewed
• [Presentation] 制御性ミエロイド細胞による炎症性腸疾患抑制機構 (2012)
  • Author(s): 香山尚子
  • Organizer: 日本臨床免疫学会
  • Place of Presentation: 東京、日本
• [Presentation] 腸管粘膜固有層における制御性ミエロイド細胞依存的な獲得免疫系制御機構 (2012)
  • Author(s): 香山尚子
  • Organizer: 日本インターフェロン・サイトカイン学会
  • Place of Presentation: 神戸・日本
• [Presentation] 腸管粘膜固有層における制御性ミエロイド細胞依存的な獲得免疫系制御機構 (2012)
  • Author(s): 香山尚子、竹田潔
  • Organizer: 第77回日本インターフェロンサイトカイン学会
  • Place of Presentation: 日本・神戸
  • Invited
• [Presentation] 制御性ミエロイド細胞による炎症性腸疾患制御機構 (2012)
  • Author(s): 香山尚子、竹田潔
  • Organizer: 第40回日本臨床免疫学会
  • Place of Presentation: 日本・東京
  • Invited
• [Presentation] Bifidobacterium breve induces IL-10-producing typeI regulatory T cell (Tr1) in the colon (2012)
  • Author(s): 香山尚子、Seong Gyu Jeon、竹田潔
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 日本・神戸
• [Presentation] Probiotic Bifidobacterium breve induces IL-10-producing Tr1 cells (2012)
  • Author(s): Hisako Kayama, Seong Gyu , Kiyoshi Takeda
  • Organizer: keystone symposia
  • Place of Presentation: アメリカ合衆国 コロラド州
• [Presentation] Regulatory myeloid cells prevent T cell dependent colitis in lamina propria (2011)
  • Author(s): Hisako Kayama
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉,日本
• [Presentation] Intestinal Gr-1highCD11b+CD11c+ cells prevent T cell dependent colitis (2011)
  • Author(s): Hisako Kayama
  • Organizer: IInternational Congress of Mucosal Immunology
  • Place of Presentation: Paris, France
• [Presentation] Regulatory myeloid cells prevent T-cell dependent colitis in lamina propria (2011)
  • Author(s): Hisako Kayama, Yoshiyasu Ueda, Kiyoshi Takeda
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉
• [Presentation] Intestinal Gr-1highCD11b+CD11c+ cells prevent T cell-dependent colitis. (2011)
  • Author(s): Hisako Kayama
  • Organizer: Inernational Congress of Mucosal Immunology
  • Place of Presentation: フランス パリ
• [Book] 炎症と免疫 巻:21 号:4 制御性ミエロイド細胞 (2013)
  • Author(s): 香山尚子・竹田潔
• [Book] 日本消化器学会雑誌 巻:110 号:5 消化管疾患と自然免疫研究の進歩 (2013)
  • Author(s): 香山尚子・竹田潔
• [Book] 医学のあゆみ 巻:246 号:11 自然免疫細胞による腸管粘膜免疫系の制御 (2013)
  • Author(s): 香山尚子・竹田潔
• [Book] 細胞工学 巻:32 号:12 自然免疫細胞による腸管免疫制御 (2013)
  • Author(s): 香山尚子・西村潤一・竹田潔
• [Book] 炎症と免疫 (2013)
  • Author(s): 香山尚子・竹田潔
  • Total Pages: 5
  • Publisher: 先端医学社
• [Book] 日本消化器学会雑誌 (2013)
  • Author(s): 香山尚子・竹田潔
  • Total Pages: 11
  • Publisher: 日本消化器学会
• [Book] 医学のあゆみ (2013)
  • Author(s): 香山尚子・竹田潔
  • Total Pages: 5
  • Publisher: 医歯薬出版株式会社
• [Book] 細胞工学 (2013)
  • Author(s): 香山尚子・西村潤一・竹田潔
  • Total Pages: 5
  • Publisher: 学研メディカル秀潤社
• [Book] 細胞工学 巻:31 号:11 制御性ミエロイド(Mreg)細胞による腸管炎症制御 (2012)
  • Author(s): 香山尚子・竹田潔
• [Book] 実験医学 巻:30 号:20 腸管粘膜における制御性ミエロイド細胞 (2012)
  • Author(s): 香山尚子・竹田潔
• [Book] 免疫学Update 腸内細菌と免疫細胞サブセット (2012)
  • Author(s): 香山尚子・竹田潔
• [Book] 免疫学Update (2012)
  • Author(s): 香山尚子、竹田潔
  • Total Pages: 7
  • Publisher: 南山堂
• [Book] 感染・共生・生体防御システム (2012)
  • Author(s): 香山尚子、竹田潔
  • Total Pages: 7
  • Publisher: 羊土社
• [Book] 細胞工学 巻:30 号:4 腸管マクロファージによる炎症制御 (2011)
  • Author(s): 香山尚子・竹田潔
• [Book] 実験医学 巻:29 号:10 自然免疫系による炎症性腸疾患制御の分子メカニズム (2011)
  • Author(s): 香山尚子・竹田潔
• [Book] IBD Resarch 巻:5 号:4 自然免疫とはなんですか? IBDの視点から (2011)
  • Author(s): 香山尚子・竹田潔
• [Book] 実験医学 (2011)
  • Author(s): 香山尚子、竹田潔
  • Total Pages: 8
  • Publisher: 自然免疫系による炎症性腸疾患制御の分子メカニズム
• [Book] IBD Reserch (2011)
  • Author(s): 香山尚子
  • Total Pages: 4
  • Publisher: 自然免疫とはなんですか？IBDの視点から