Fibrocyte浸潤による腸管線維化機序の解明と新規治療標的の探索

• 研究課題/領域番号: 24659374
• 研究種目: 挑戦的萌芽研究
• 配分区分: 基金
• 研究分野: 消化器内科学
• 研究機関: 慶應義塾大学
• 研究代表者: 日比 紀文 慶應義塾大学, 医学部, 教授 (50129623)
• 研究期間 (年度): 2012
• 研究課題ステータス: 完了 (2012年度)
• 配分額: 3,770千円 (直接経費: 2,900千円、間接経費: 870千円); 2012年度: 3,770千円 (直接経費: 2,900千円、間接経費: 870千円)
• キーワード: クローン病 / 腸管線維化 / fibrocyte

研究概要

我々はこの1年間でクローン病患者末梢血中にfibrocyteが増加していることを見出した。現在、患者背景因子と末梢血fibrocyteの相関を解析し線維化リスク因子の割り出しに着手している。さらにfibrocyteを標的とした線維化予防治療の開発のため腸管線維化モデルの開発に着手した。また末梢血fibrocyteのダイナミクスをより詳細に解析するためcollagen-GFPマウスをすでに手に入れており、今後DSS腸炎での末梢血fibrocyteの可視化を試みるとともに、isolationしてその機能解析に取り組む予定である。またよりクローン病に近いモデルとしてTNFΔAREマウスをギリシアから入手しており、同マウスにおいてcollagen産生fibrocyteの動態が他のモデルとどう異なっているのかを解析している。

研究成果

• [雑誌論文] CCR2 knockout exacerbates cerulein-induced chronic pancreatitis with hyperglycemia via decreased GLP-1 receptor expression and insulin secretion (2013)
  • 著者名/発表者名: Nakamura Y, Kanai T, Saeki K, Takabe M, Irie J, Miyoshi J, Mikami Y, Teratani T, Suzuki T, Miyata N, Hisamatsu T, Nakamoto N, Yamagishi Y, Higuchi H, Ebinuma H, Hozawa S, Saito H, Itoh H, Hibi T
  • 雑誌名: Am J Physiol Gastrointest Liver Physiol
  • 査読あり
• [雑誌論文] Dendritic cells administered intrarectally penetrate the intestinal barrier to break intestinal tolerance via Th2-medeiated colitis in mice (2013)
  • 著者名/発表者名: Handa T, Kanai T, Sato T, Mikami Y, Sujino T, Hayashi A, Mizuno S, Matsumoto A, Hisamatsu T, Hibi T.
  • 雑誌名: Immunol Lett.
  • 査読あり
• [雑誌論文] CCR2 knockout exacerbates cerulein-induced chronic pancreatitis with hyperglycemia via decreased GLP-1 receptor expression and insulin secretion. (2013)
  • 著者名/発表者名: Nakamura Y, Kanai T, Saeki K, Takabe M, Irie J, Miyoshi J, Mikami Y, Teratani T, Suzuki T, Miyata N, Hisamatsu T, Nakamoto N, Yamagishi Y, Higuchi H, Ebinuma H, Hozawa S, Saito H, Itoh H, Hibi T.
  • 雑誌名: Am J Physiol Gastrointest Liver Physiol 巻: 304 号: 8 ページ: G700-G707
  • DOI: 10.1152/ajpgi.00318.2012
  • 査読あり
• [雑誌論文] Dendritic cells administered intrarectally penetrate the intestinal barrier to break intestinal tolerance via Th2-medeiated colitis in mice. (2013)
  • 著者名/発表者名: Handa T, Kanai T, Sato T, Mikami Y, Sujino T, Hayashi. A, Mizuno S, Matsumoto A, Hisamatsu T, Hibi T.
  • 雑誌名: Immunology Letters 巻: 150 号: 1-2 ページ: 123-9
  • DOI: 10.1016/j.imlet.2013.01.010
  • 査読あり
• [雑誌論文] TGR5 signalling inhibits the production of pro-inflammatory cytokines by in vitro differentiated inflammatory and intestinal macrophages in Crohn's disease. (2013)
  • 著者名/発表者名: Yoneno K, Hisamatsu T, Shimamura K, Kamada N, Ichikawa R, Kitazume MT, Mori M, Uo M, Namikawa Y, Matsuoka K, Sato T, Koganei K, Sugita A, Kanai T, Hibi T.
  • 雑誌名: Immunology 巻: 139(1) 号: 1 ページ: 19-29
  • DOI: 10.1111/imm.12045
  • 査読あり
• [雑誌論文] Immune aspects of the pathogenesis of inflammatory bowel disease (2012)
  • 著者名/発表者名: Hisamatsu T, Kanai T, Yohei Mikami, Yoneno K, Matsuoka K, Hibi T
  • 雑誌名: Pharmacol Ther.
  • 査読あり
• [雑誌論文] Dysregulated balance of retinoid-related orphan receptor γt-dependent innate lymphoid cells is involved in the pathogenesis of chronic DSS-induced colitis (2012)
  • 著者名/発表者名: Kimura K, Kanai T, Hayashi A, Mikami Y, Sujino T, Mizuno S, Handa T, Matsuoka K, Hisamatsu T, Sato T Hibi T
  • 雑誌名: Biochem Biophys Res Commun 巻: 427 ページ: 694-700
  • 査読あり
• [雑誌論文] T-helper 17 and Interleukin-17-Producing Lymphoid Tissue Inducer-Like T Cells Make Different Contributions to Colitis in Mice (2012)
  • 著者名/発表者名: Ono Y, Kanai T, Sujino T, Nemoto Y, Kanai Y, Mikami Y, Hayashi A, Matsumoto A, Takaishi H, Ogata H, Matsuoka K, Hisamatsu T, Watanabe M, Hibi T .
  • 雑誌名: Gastroenterology. 巻: 143 ページ: 1288-97
  • 査読あり
• [雑誌論文] Mucosal CXCR4+ IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14+ macrophage activation (2012)
  • 著者名/発表者名: Uo M, Hisamatsu T, Miyoshi J, Kaito D, Yoneno K, Kitazume MT, Mori M, Sugita A, Koganei K,Matsuoka K, Kanai T, Hibi T
  • 雑誌名: Gut.
  • 査読あり
• [雑誌論文] Is the dendritic cell a missing piece in the pathogenesis model of post-infectious irritable bowel syndrome?-Editorial for "Characteristics of intestinal lamina propria dendritic cells in a mouse model of postinfectious irritable bowel syndrome. (2012)
  • 著者名/発表者名: Hisamatsu T, Hibi T
  • 雑誌名: J Gastroenterol Hepatol. 巻: 27 ページ: 847-8
  • 査読あり
• [雑誌論文] A Case of Intestinal Behcet's Disease Treated with Infliximab Monotherapy Who Successfully Maintained Clinical Remission and Complete Mucosal Healing for Six Years (2012)
  • 著者名/発表者名: Maruyama Y, Hisamatsu T, Matsuoka K, Naganuma M, Inoue N, Ogata H, Iwao Y, Kanai T, Hibi T
  • 雑誌名: Intern Med 巻: 51 ページ: 2125-9
  • 査読あり
• [雑誌論文] Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells. (2012)
  • 著者名/発表者名: Nishida A, Nagahama K, Imaeda H, Ogawa A, Lau CW, Kobayashi T, Hisamatsu T, Preffer FI, Mizoguchi E, Ikeuchi H, Hibi T, Fukuda M, Andoh A, Blumberg RS, Mizoguchi A.
  • 雑誌名: J Exp Med. 巻: 209(13) 号: 13 ページ: 2383-94
  • DOI: 10.1084/jem.20112631
  • 査読あり
• [雑誌論文] Anticoagulation therapy dramatically improved severe sigmoiditis with findings resembling inflammatory bowel disease, which was caused by mesenteric venous thrombosis. (2012)
  • 著者名/発表者名: Mikami Y, Kanai T, Iwasaki E, Naganuma M, Yamagishi Y, Shimoda M, Matsuoka K, Hisamatsu T, Iwao Y, Ogata H, Nakatsuka S, Mukai M, Hibi T.
  • 雑誌名: Clinical Journal of Gastroenterology. 巻: 5 ページ: 377-382
  • 査読あり
• [雑誌論文] Immune aspects of the pathogenesis of inflammatory bowel disease. (2012)
  • 著者名/発表者名: Hisamatsu T, Kanai T, Mikami Y, Yoneno K, Matsuoka K, Hibi T.
  • 雑誌名: Pharmacology & Therapeutics 巻: 137 号: 3 ページ: 283-297
  • DOI: 10.1016/j.pharmthera.2012.10.008
  • 査読あり
• [雑誌論文] Activated Hepatic Stellate Cells Mediate the Differentiation of Macrophages. (2012)
  • 著者名/発表者名: Chang J, Hisamatsu T, Shimamura K, Yoneno K, Adachi M, Naruse H, Igarashi T, Higuchi H, Matsuoka K, Kitazume MT, Ando S, Kamada N, Kanai T, and Hibi T.
  • 雑誌名: Hepatology Research. 巻: Epub ahead of print 号: 6 ページ: 658-669
  • DOI: 10.1111/j.1872-034x.2012.01111.x
  • NAID: 10031194568
  • 査読あり
• [雑誌論文] Dysregulated balance of retinoid-related orphan receptor _Yt-dependent innate lymphoid cells is involved in the pathogenesis of chronic DSS-induced colitis. (2012)
  • 著者名/発表者名: Kimura K, Kanai T, Hayashi A, Mikami Y, Sujino T, Mizuno S, Handa T, Matsuoka K, Hisamatsu T, Sato T, Hibi T.
  • 雑誌名: Biochemical and Biophysical Research Communications 巻: 427 号: 4 ページ: 694-700
  • DOI: 10.1016/j.bbrc.2012.09.091
  • 査読あり
• [雑誌論文] Mucosal CXCR4+ IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14+ macrophage activation. (2012)
  • 著者名/発表者名: Uo M, Hisamatsu T, Miyoshi J, Kaito D, Yoneno K, Kitazume MT, Mori M, Sugita A, Koganei K,Matsuoka K, Kanai T, Hibi T.
  • 雑誌名: Gut. 巻: Epub ahead of print
  • 査読あり
• [雑誌論文] A Case of Intestinal Behçet's Disease Treated with Infliximab Monotherapy Who Successfully Maintained Clinical Remission and Complete Mucosal Healing for Six Years. (2012)
  • 著者名/発表者名: Maruyama Y, Hisamatsu T, Matsuoka K, Naganuma M, Inoue N, Ogata H, Iwao Y, Kanai T, Hibi T.
  • 雑誌名: Intern Med. 巻: 51(16) ページ: 2125-9
  • NAID: 130002062319
  • 査読あり
• [雑誌論文] T-helper 17 and Interleukin-17-Producing Lymphoid Tissue Inducer-Like T Cells Make Different Contributions to Colitis in Mice. (2012)
  • 著者名/発表者名: Ono Y, Kanai T, Sujino T, Nemoto Y, Kanai Y, Mikami Y, Hayashi A, Matsumoto A, Takaishi H, Ogata H, Matsuoka K, Hisamatsu T, Watanabe M, Hibi T.
  • 雑誌名: Gastroenterology 巻: 143 号: 5 ページ: 1288-1297
  • DOI: 10.1053/j.gastro.2012.07.108
  • 査読あり
• [雑誌論文] Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells
  • 著者名/発表者名: Nishida A, Nagahama K, Imaeda H, Ogawa A, Lau CW, Kobayashi T, Hisamatsu T, Preffer FI, Mizoguchi E, Ikeuchi H, Hibi T, Fukuda M, Andoh A, Blumberg RS, Mizoguchi A
  • 雑誌名: J Exp Med 巻: (in press)
  • 査読あり
• [雑誌論文] TGR5 signaling inhibits the production of pro-inflammatory cytokines by in vitro differentiated inflammatory and intestinal macrophages in Crohn's disease
  • 著者名/発表者名: Yoneno K, Hisamatsu T, Shimamura K, Kamada N, Ichikawa R, Kitazume MT, Mori M, Uo M, Namikawa Y, Matsuoka K, Sato T, KoganeiK, Sugita A, Kanai T, Hibi T
  • 雑誌名: Immunology 巻: (in press)
  • 査読あり
• [雑誌論文] Anticoagulation therapy dramatically improved severe sigmoiditis with findings resembling inflammatory bowel disease, which was caused by mesenteric venous thrombosis
  • 著者名/発表者名: Mikami Y, Kanai T, Iwasaki E, Naganuma M, Yamagishi Y, Shimoda M, Matsuoka K, Hisamatsu T, Iwao Y, Ogata H, Nakatsuka S, Mukai M, Hibi T
  • 雑誌名: Clinical Journal of Gastroenterology 巻: (in press)
  • 査読あり
• [雑誌論文] Activated Hepatic Stellate Cells Mediate the Differentiation of Macrophages.
  • 著者名/発表者名: Chang J, Hisamatsu T, Shimamura K, Yoneno K, Adachi M, Naruse H, Igarashi T, Higuchi H, Matsuoka K, Kitazume MT, Ando S, Kamada N, Kanai T, and Hibi T
  • 雑誌名: Hepatology Research 巻: (in press)
  • NAID: 10031194568
  • 査読あり
• [学会発表] Early normalization of C-reactive protein (CRP)by infliximab is a predictive factor of sustained longterm clinical efficacy in crohn's disease. (2012)
  • 著者名/発表者名: Kimura K, Matsuoka K, Kanai T, Okamoto S,Hisamatsu T, Inoue N, Yajima T, Ogata H, I wa o Y, Hibi T
  • 学会等名: The 14th Meeting of International Conference on Ulcer Research
  • 発表場所: Tokyo
  • 年月日: 2012-07-14
• [学会発表] Early normalization of C-reactive protein (CRP)by infliximab is a predictive factor of sustained long-term clinical efficacy in crohn’s disease. (2012)
  • 著者名/発表者名: 26. Kimura K, Matsuoka K, Kanai T, Okamoto S, Hisamatsu T, Inoue N, Yajima T, Ogata H, Iwao Y, Hibi T
  • 学会等名: The 14th Meeting of International Conference on Ulcer Research.
  • 発表場所: Tokyo