Analysis of innate immune cells in small intestinal lamina propria

• Project/Area Number: 24590582
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: The University of Tokyo
• Principal Investigator: UEMATSU Satoshi 東京大学, 医科学研究所, 特任教授 (50379088)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 粘膜免疫 / 自然免疫 / Toll-like receptor / 腸管粘膜固有層 / 樹状細胞 / マクロファージ

Outline of Final Research Achievements

We examined expression of TLR family members and cytokine production in macrophage of small intestinel lamina propria. We analyzed dendritic cells in small intestinel lamina propria to develop a new vaccine which can induce mucosal IgA. We also clarified that TLR3 is an exacerbating factor for radiation-induced acute intestinal injury by using TLR3-deficient mice. We further clarified that eosinophils play essential roles for intestinal fibrosis after abdominal irradiation.

Research Products

• [Journal Article] 5-azacytidine-induced protein 2 (AZI2) regulates bone mass by fine-tuning osteoclast survival. (2015)
  • Author(s): Maruyama K, Fukasaka M, Uematsu S, Takeuchi O, Kondo T, Saitoh T, Martino M, Akira S.
  • Journal Title: J Biol Chem. Volume: pii: jbc.M114.631374. Pages: 1-19
  • Peer Reviewed / Open Access
• [Journal Article] MyD88 Signaling Inhibits Protective Immunity to the Gastrointestinal Helminth Parasite Heligmosomoides polygyrus. (2014)
  • Author(s): Reynolds LA, Harcus Y, Smith KA, Webb LM, Hewitson JP, Ross EA, Brown S, Uematsu S, Akira S, Gray D, Gray M, MacDonald AS, Cunningham AF, Maizels RM.
  • Journal Title: J Immunol. Volume: 193(6) Issue: 6 Pages: 2984-93
  • DOI: 10.4049/jimmunol.1401056
  • Peer Reviewed / Open Access
• [Journal Article] Innate lymphoid cells regulate intestinal epithelial cell glycosylation. (2014)
  • Author(s): Goto Y, Obata T, Kunisawa J, Sato S, Ivanov II, Lamichhane A, Takeyama N, Kamioka M, Sakamoto M, Matsuki T, Uematsu S, Akira S, Domino SE, Kulig P, Becher B, Renauld JC, Sasakawa C, Umesaki Y, Benno Y, Kiyono H
  • Journal Title: Science Volume: 345 Issue: 6202 Pages: 1254009-1254009
  • DOI: 10.1126/science.1254009
  • Peer Reviewed / Open Access
• [Journal Article] Rapid CD4+ T-cell responses to bacterial flagellin require dendritic cell expression of Syk and CARD9. (2014)
  • Author(s): Atif SM, Lee SJ, Li LX, Uematsu S, Akira S, Gorjestani S, Lin X, Schweighoffer E, Tybulewicz VL, McSorley SJ.
  • Journal Title: Eur J Immunol. Volume: 45(2) Issue: 2 Pages: 513-24
  • DOI: 10.1002/eji.201444744
  • Peer Reviewed / Open Access
• [Journal Article] Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome. (2014)
  • Author(s): Takemura, N., et al.
  • Journal Title: Nature Commun. Volume: 5 Issue: 1 Pages: 3492-3492
  • DOI: 10.1038/ncomms4492
  • Peer Reviewed
• [Journal Article] Prevention of intestinal allergy in mice by rflaA:Ova is associated with enforced antigen processing and TLR5-dependent IL-10 secretion by mDC. (2014)
  • Author(s): Schülke S, Wolfheimer S, Gadermaier G, Wangorsch A, Siebeneicher S, Briza P, Spreitzer I, Schiller D, Loeschner B, Uematsu S, Ryffel B, Akira S, Waibler Z, Vieths S, Toda M, Scheurer S.
  • Journal Title: PLoS One. Volume: 9(2) Issue: 2 Pages: e87822-e87822
  • DOI: 10.1371/journal.pone.0087822
  • Peer Reviewed
• [Journal Article] rostaglandin E₂ is critical for the development of niacin-deficiency-induced photosensitivity via ROS production. (2013)
  • Author(s): Sugita K, Ikenouchi-Sugita A, Nakayama Y, Yoshioka H, Nomura T, Sakabe J, Nakahigashi K, Kuroda E, Uematsu S, Nakamura J, Akira S, Nakamura M, Narumiya S, Miyachi Y, Tokura Y, Kabashima K
  • Journal Title: Scientific reports Volume: 3 Issue: 1 Pages: 2973-2973
  • DOI: 10.1038/srep02973
  • Peer Reviewed
• [Journal Article] Increased Th17-inducing activity of CD14+ CD163low myeloid cells in intestinal lamina propria of patients with Crohn's disease. (2013)
  • Author(s): Ogino T, Nishimura J, Barman S, Kayama H, Uematsu S, Okuzaki D, Osawa H, Haraguchi N, Uemura M, Hata T, Takemasa I, Mizushima T, Yamamoto H, Takeda K, Doki Y, Mori M.
  • Journal Title: Gastroenterology Volume: 145(6) Issue: 6 Pages: 1380-1391
  • DOI: 10.1053/j.gastro.2013.08.049
  • Peer Reviewed
• [Journal Article] Flagellin enhances tumor-specific CD8⁺ T cell immune responses through TLR5 stimulation in a therapeutic cancer vaccine model. (2013)
  • Author(s): Nguyen CT, Hong SH, Sin JI, Vu HV, Jeong K, Cho KO, Uematsu S, Akira S, Lee SE, Rhee JH.
  • Journal Title: Vaccine. Volume: 31(37) Issue: 37 Pages: 3879-87
  • DOI: 10.1016/j.vaccine.2013.06.054
  • Peer Reviewed
• [Journal Article] Double-stranded RNA of small intestinal commensal but not pathogenic bacteria triggers TLR3-mediated IFN-β production by dendritic cells (2013)
  • Author(s): T. Kawashima, A. Kosaka, H. Yan, G. Zijin, R. Uchiyama, R. Fukui, D. Kaneko; Y. Kumagai; D.-J. You, J. Carreras, S. Uematsu, M. H. Jang, O. Takeuchi, T. Kaisho, S. Akira, K. Miyake, H. Tsutsui, T. Saito, I. Nishimura, N. M. Tsuji
  • Journal Title: Immunity Volume: 38 Issue: 6 Pages: 1187-1197
  • DOI: 10.1016/j.immuni.2013.02.024
  • Peer Reviewed
• [Journal Article] Critical Role of AZI2 in GM-CSF-Induced Dendritic Cell Differentiation (2013)
  • Author(s): Fukasaka M, Ori D, Kawagoe T, Uematsu S, Maruyama K, Okazaki T, Kozaki T, Imamura T, Tartey S, Mino T, Satoh T, Akira S, Takeuchi O
  • Journal Title: J Immunol Volume: 190 Issue: 11 Pages: 5702-11
  • DOI: 10.4049/jimmunol.1203155
  • Peer Reviewed
• [Journal Article] Toll-like receptor 7 gene deficiency and early-life Pneumovirus infection interact to predispose toward the development of asthma-like pathology in mice. (2013)
  • Author(s): Kaiko GE, Loh Z, Spann K, Lynch JP, Lalwani A, Zheng Z, Davidson S, Uematsu S, Akira S, Hayball J, Diener KR, Baines KJ, Simpson JL, Foster PS, Phipps S.
  • Journal Title: J Allergy Clin Immunol. Volume: 131(5) Issue: 5 Pages: 1331-9
  • DOI: 10.1016/j.jaci.2013.02.041
  • Peer Reviewed
• [Journal Article] Microsomal prostaglandin E synthase-1 is induced in Alzheimer's disease and its deletion mitigates Alzheimer's disease-like pathology in a mouse model (2013)
  • Author(s): Akitake Y, Nakatani Y, Kamei D, Hosokawa M, Akatsu H, Uematsu S, Akira S, Kudo I, Hara S, Takahashi M
  • Journal Title: J. Neurosci. Res Volume: 91(7) Issue: 7 Pages: 909-919
  • DOI: 10.1002/jnr.23217
  • Peer Reviewed
• [Journal Article] Bacterial sphingophospholipids containing non-hydroxy fatty acid activate murine macrophages via Toll-like receptor 4 and stimulate bacterial clearance. (2013)
  • Author(s): Fujiwara N, Porcelli SA, Naka T, Yano I, Maeda S, Kuwata H, Akira S, Uematsu S, Takii T, Ogura H, Kobayashi K.
  • Journal Title: iochim Biophys Acta. Volume: 1831(6) Pages: 1177-84
  • Peer Reviewed
• [Journal Article] Microsomal prostaglandin E synthase-1 aggravates inflammation and demyelination in a mouse model of multiple sclerosis. (2013)
  • Author(s): Takeuchi C, Matsumoto Y, Kohyama K, Uematsu S, Akira S, Yamagata K and Takemiya T.
  • Journal Title: Neurochem Int. Volume: 62 Issue: 3 Pages: 271-280
  • DOI: 10.1016/j.neuint.2012.12.007
  • Peer Reviewed
• [Journal Article] Bacterial sphingophospholipids containing non-hydroxy fatty acid activate murine macrophages via Toll-like receptor 4 and stimulate bacterial clearance (2013)
  • Author(s): Fujiwara, N.
  • Journal Title: Biochim. Biophys. Acta. Volume: Mar 29 Issue: 6 Pages: 1177-84
  • DOI: 10.1016/j.bbalip.2013.03.008
  • Peer Reviewed
• [Journal Article] Critical role of microsomal prostaglandin E synthase-1 in the hydronephrosis caused by lactational exposure to dioxin in mice (2012)
  • Author(s): Yoshioka W, Aida-Yasuoka K, Fujisawa N, Kawaguchi T, Ohsako S, Hara S, Uematsu S, Akira S, Tohyama C
  • Journal Title: Toxicol. Sci Volume: 127(2) Issue: 2 Pages: 547-554
  • DOI: 10.1093/toxsci/kfs115
  • Peer Reviewed
• [Journal Article] Leukemia inhibitory factor coordinates the down-regulation of the visual cycle in the retina and retinal-pigmented epithelium. (2012)
  • Author(s): Chucair-Elliott AJ, Elliott MH, Wang J, Moiseyev GP, Ma JX, Politi LE, Rotstein NP, Akira S, Uematsu S, Ash JD.
  • Journal Title: J Biol Chem. Volume: 287(29) Issue: 29 Pages: 24092-102
  • DOI: 10.1074/jbc.m112.378240
  • Peer Reviewed
• [Journal Article] Deletion of microsomal prostaglandin E synthase-1 protects neuronal cells from cytotoxic effects of β-amyloid peptide fragment31-35 (2012)
  • Author(s): Kuroki Y, Sasaki Y, Kamei D, Akitake Y, Takahashi M, Uematsu S, Akira S, Nakatani Y, Kudo I, Hara S
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 424(3) Issue: 3 Pages: 409-413
  • DOI: 10.1016/j.bbrc.2012.06.121
  • Peer Reviewed
• [Journal Article] Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity. (2012)
  • Author(s): Kreutz M, Giquel B, Hu Q, Abuknesha R, Uematsu S, Akira S, Nestle FO, Diebold SS.
  • Journal Title: PLoS One. Volume: 7(7) Issue: 7 Pages: e40208-e40208
  • DOI: 10.1371/journal.pone.0040208
  • Peer Reviewed
• [Journal Article] PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells. (2012)
  • Author(s): Shibata T, Takemura N, Motoi Y, Goto Y, Karuppuchamy T, Izawa K, Li X, Akashi-Takamura S, Tanimura N, Kunisawa J, Kiyono H, Akira S, Kitamura T, Kitaura J, Uematsu S, Miyake K.
  • Journal Title: Int Immunol. Volume: 24(10) Pages: 613-23
  • Peer Reviewed
• [Journal Article] Systemic flagellin immunization stimulates mucosal CD103+ dendritic cells and drives Foxp3+ regulatory T cell and IgA responses in the mesenteric lymph node. (2012)
  • Author(s): Flores-Langarica A, Marshall JL, Hitchcock J, Cook C, Jobanputra J, Bobat S, Ross EA, Coughlan RE, Henderson IR, Uematsu S, Akira S, Cunningham AF.
  • Journal Title: J Immunol. Volume: 189(12) Issue: 12 Pages: 5745-54
  • DOI: 10.4049/jimmunol.1202283
• [Presentation] Innate immune responses in radiation-induced intestinal injury. (2014)
  • Author(s): Satoshi Uematsu
  • Organizer: The 1st Symposium of Max Planck-The University of Tokyo Center for Integrative Inflammology.
  • Place of Presentation: Berlin, Germany.
  • Year and Date: 2014-12-17 – 2014-12-18
• [Presentation] Innate immune responses in radiation-induced intestinal injury. (2014)
  • Author(s): Satoshi Uematsu
  • Organizer: Novo Nordisk Innovation Summit.
  • Place of Presentation: Tokyo
  • Year and Date: 2014-10-01
• [Presentation] Resident myofibroblasts and eosinophils mediate radiation-induced intestinal fibrosis. (2014)
  • Author(s): Satoshi Uematsu, Naoki Takemura.
  • Organizer: The 13th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Nara, Japan.
  • Year and Date: 2014-09-23 – 2014-09-25
• [Presentation] Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome. (2014)
  • Author(s): Satoshi Uematsu.
  • Organizer: The 2nd Symposium of International Immunological Memory and Vaccine Forum.
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-08-24 – 2014-08-25
• [Presentation] 粘膜アジュバント標的細胞. (2013)
  • Author(s): 植松 智
  • Organizer: 第２３回感染研シンポジウム
  • Place of Presentation: 国立感染症研究所 共用第一会議室
  • Invited
• [Presentation] TLR3 /dsRNA complex inhibitor protects mice from lethal radiation-induced gastrointestinal syndrome. (2013)
  • Author(s): 植松 智, 武村直紀, 審良静男.
  • Organizer: 第12回淡路島 感染症免疫フォーラム
  • Place of Presentation: 淡路夢舞台国 際会議場
  • Invited
• [Presentation] TLR3 as an Exacerbating Factor for Radiation-induced Gastrointestinal Syndrome. (2013)
  • Author(s): Satoshi Uematsu.
  • Organizer: 15th INTERNATIONAL CONGRESS OF IMMUNOLOGY.
  • Place of Presentation: Milan, Italy.
• [Presentation] Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome. (2013)
  • Author(s): Satoshi Uematsu.
  • Organizer: Annual meeting of French Society for Immunology 2013.
  • Place of Presentation: Paris, France.
  • Invited
• [Presentation] 腸管粘膜固有層の自然免疫細胞群の機能解析. (2013)
  • Author(s): 植松 智
  • Organizer: 第155回日本獣医学会学術集会 日本比較薬理学・毒性学会
  • Place of Presentation: 東京大学駒場キャンパス
  • Invited
• [Presentation] 自然免疫受容体と腸管免疫応答. (2012)
  • Author(s): 植松 智
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京 京王プラザホテル
  • Invited
• [Presentation] 腸管粘膜固有層の自然免疫細胞群の機能解析 (2012)
  • Author(s): 植松 智
  • Organizer: 第21回内毒素・LPS研究会
  • Place of Presentation: 東京大学医学部
  • Invited
• [Book] 急性放射線性消化管症候群におけるToll様受容体の役割. (2015)
  • Author(s): 武村 直紀, 植松 智.
  • Total Pages: 14
  • Publisher: 放射線生物研究
• [Book] TLR3を介した放射線誘導性腸上皮傷害機構. (2014)
  • Author(s): 武村 直紀, 植松 智.
  • Total Pages: 7
  • Publisher: Isotope News 〔No.727〕
• [Book] 放射線誘導性腸上皮傷害における増悪因子としてのTLR3の役割. (2014)
  • Author(s): 武村 直紀, 植松 智.
  • Total Pages: 12
  • Publisher: 日本インターフェロン・サイトカイン学会ニュースレター
• [Remarks] TLR3の阻害が致死的な放射線誘導性腸炎を著しく改善させる
  • URL: http://www.ims.u-tokyo.ac.jp/imsut/jp/research/papers/tlr3.php
• [Patent(Industrial Property Rights)] PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING RADIATION-INDUCED GASTROINTENSTINAL SYNDOROME (2013)
  • Inventor(s): 植松智、武村直紀、審良静男
  • Industrial Property Rights Holder: 植松智、武村直紀、審良静男
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-07-30
  • Overseas