Steatohepatitis as altered immune metabolism by Regulatory T cell

• Project/Area Number: 23790791
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Osaka University
• Principal Investigator: HAMAGUCHI Masahide 大阪大学, 免疫学フロンティア研究センター, 特任助教 (80350883)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 非アルコール性脂肪肝炎 / 非アルコール性脂肪疾患 / 制御性T細胞 / 慢性炎症 / インスリン抵抗性 / レプチン抵抗性 / 非アルコール性脂肪肝疾患 / 消化器内科学 / 免疫学 / 自己免疫 / 自然炎症 / 脂肪肝

Research Abstract

Chronic inflammation is now considered to have a pivotal role in the metabolic abnormality. In liver, steatohepatitis has been recognized as the hallmarks of chronic inflammation. However, the mechanisms underlying the progression from simple steatosis to steatohepatitis have not clarified yet. Here, we showed that immune supressive activity by Treg cells were impaired under high leptin condition and steatohepatitis was observed under the condition of temporally liver regulatory T (Treg) cells depletion combined with high fat diet (HFD). Taken together, altered immune metabolism by Regulatory T cell due to leptin resistance in subjects with over nutrition or obesity could be a pathogen for the development of Steatohepatitis.

Research Products

• [Journal Article] An atlas of active enhancers across human cell types and tissues. (2014)
  • Author(s): Anderson R, Gebhard C, Miguel-Escalada I, Hoof I, Bornholdt J, Boyd M, Chen Y, Zhao X, Schmidl C, Suzuki T, Collaborators(261) Enomoto H, etc.
  • Journal Title: Nature Volume: 507 Issue: 7493 Pages: 455-461
  • DOI: 10.1038/nature12787
  • Peer Reviewed / Open Access
• [Journal Article] A promoter-level mammalian expression atlas. (2014)
  • Author(s): Forrest, A.R.R., Kawaji, H., Rehli, M., Baillie, J.K, de Hoon, M.J.L., Haberle, V., Lassmann, T., Kulakovskiy, I.V., Lizio, M., Itoh, M., Andersson, R., Mungall, C. J.,et al.
  • Journal Title: Nature Volume: 507 Issue: 7493 Pages: 462-470
  • DOI: 10.1038/nature13182
  • Peer Reviewed / Open Access
• [Journal Article] Favorable effect of modest alcohol consumption to fatty liver disease. (2013)
  • Author(s): Hamaguchi M, Kojima T
  • Journal Title: World J Gastroenterol Volume: 19 Issue: 32 Pages: 5393-4
  • DOI: 10.3748/wjg.v19.i32.5393
  • Peer Reviewed
• [Journal Article] Diabetes and colorectal cancer (2012)
  • Author(s): Hamaguchi M, Kojima T, Kato T
  • Journal Title: Nihon Rinsho Volume: Suppl 5 Pages: 573-7
• [Journal Article] T cell receptor stimulation-induced epi genetic changes and Foxp3 expression are independent and complementary events required for Treg cell development (2012)
  • Author(s): 大倉永也
  • Journal Title: Immunity Volume: 37 Issue: 5 Pages: 785-799
  • DOI: 10.1016/j.immuni.2012.09.010
  • Peer Reviewed
• [Journal Article] Regulatory T Cells Expressing PPAR-γ Control Inflammation in Obesity. (2012)
  • Author(s): Hamaguchi, Masahide, and Shimon Sakaguchi
  • Journal Title: Cell metabolism Volume: 16 Issue: 1 Pages: 4-6
  • DOI: 10.1016/j.cmet.2012.06.007
  • Peer Reviewed
• [Journal Article] Identification of individuals with non-alcoholic fatty liver disease by the diagnostic criteria for the metabolic syndrome (2012)
  • Author(s): Hamaguchi M, Takeda N, Kojima T, Ohbora A, Kato T, Sarui H, Fukui M, Nagata C, Takeda J
  • Journal Title: World J Gastroenterol Volume: 18(13) Issue: 13 Pages: 1508-16
  • DOI: 10.3748/wjg.v18.i13.1508
• [Journal Article] Aging is a risk factor of nonalcoholic fatty liver disease in premenopausal women (2012)
  • Author(s): Hamaguchi M, Kojima T, Ohbora A, Takeda N, Fukui M, Kato T
  • Journal Title: World J Gastroenterol Volume: 18(3) Issue: 3 Pages: 237-43
  • DOI: 10.3748/wjg.v18.i3.237
• [Journal Article] Protective effect of alcohol consumption for fatty liver but not metabolic syndrom (2012)
  • Author(s): kui,Takahiro Kato
  • Journal Title: World of Gastroenterology Volume: 18(2) Issue: 2 Pages: 156-167
  • DOI: 10.3748/wjg.v18.i2.156
  • Peer Reviewed
• [Journal Article] Diabetes and Colorectal Cancer (2012)
  • Author(s): Hamaguchi, Masahide, Takao Kojima, and Takahiro Kato
  • Journal Title: Nihon rinsho Volume: 70 Suppl 5 Pages: 573-577
• [Journal Article] Association between Bright Pancreas and Features of Metabolic Syndrome (2012)
  • Author(s): Akihiro Ohbora, Takao Kojima, Takahiro Kato, Mio Endo, Kiichiro Miyawaki, Nobuhiro Fukuta, Naomi Ban, Masahide Hamaguchi
  • Journal Title: Ningen Dock Volume: 26（6） Pages: 935-943
  • NAID: 10031145832
  • Peer Reviewed
• [Journal Article] Aging is a risk factor of nonalcoholic fatty liver disease in premenopausal women. (2012)
  • Author(s): Hamaguchi M, Kojima T, Ohbora A, Takeda N, Fukui M, Kato T.
  • Journal Title: World J Gastroenterol. Volume: 3 Pages: 237-43
  • Peer Reviewed
• [Journal Article] Protective effect of alcohol consumption for fatty liver but not metabolic syndrome. (2012)
  • Author(s): Hamaguchi M, Kojima T, Ohbora A, Takeda N, Fukui M, Kato T.
  • Journal Title: World J Gastroenterol. Volume: 2 Pages: 156-67
  • Peer Reviewed
• [Journal Article] Identification of individuals with non-alcoholic fatty liver disease by the diagnostic criteria for the metabolic syndrome. (2012)
  • Author(s): Hamaguchi M, Takeda N, Kojima T, Ohbora A, Kato T, Sarui H, Fukui M, Nagata C, Takeda J.
  • Journal Title: World J Gastroenterol. Volume: 13 Pages: 1508-16
  • Peer Reviewed
• [Presentation] 東京制御性T細胞減弱による代謝免疫学的非アルコール性脂肪肝炎(NASH)モデルマウスの解析 (2014)
  • Author(s): 濱口真英、島津裕、高折晃史、角田圭雄、山口寛二、西川博嘉、福井道明、坂口志文、伊藤義人、中村直登
  • Organizer: 第1回肝臓と糖尿病・代謝研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-04
• [Presentation] Essential role for BCL11b in the FoxP3 transcriptional complex and T regulatory cells suppressive function (2013)
  • Author(s): Masahide Hamaguchi, Kaoru Sakai, Naganari Ohkura, Hiromasa Morikawa, Yutaka Shimazu, James Badger Wing, Shimon Sakaguchi
  • Organizer: 国際免疫学会
  • Place of Presentation: ミラノ、イタリア
• [Presentation] 岐阜における非アルコール性脂肪肝NAFLDの経時的コホート研究
  • Author(s): 濱口真英、小島孝雄、大洞昭博
  • Organizer: NAGALA (NAFLD in Gifu Area, Longitudinal Analysis) study
• [Presentation] 制御性T細胞減弱による代謝免疫学的非アルコール性脂肪肝炎(NASH)モデルマウスの解析
  • Author(s): 濱口真英、島津裕、高折晃史、角田圭雄、山口寛二、西川博嘉、福井道明、坂口志文、伊藤義人、中村直登
  • Organizer: 第1回肝臓と糖尿病・代謝研究会
  • Place of Presentation: 東京
• [Presentation] Transcriptional complexes containing Foxp3 and Bcl11b control Treg supressive function
  • Author(s): Masahide Hamaguchi, Kaoru Sakai, Naganari Ohkura, Hiromasa Morikawa1, Yutaka Shimazu1, Shimon Sakaguchi
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 神戸市神戸国際会議場
• [Presentation] Constitution of the Foxp3 complex: key association of Bcl11b to CTLA-4 dependent Treg supressive function
  • Author(s): Masahide Hamaguchi, Kaoru Sakai, Naganari Ohkura, Hiromasa Morikawa1, Yutaka Shimazu1, Hans Joerg Fehling, Tim Sparwasser, Tetsuya Hirose, Ryo KominamiShimon Sakaguchi
  • Organizer: The 2nd NIF Winter School on Advanced Immunology
  • Place of Presentation: Singapore, Amara Sanctury resort
• [Book] リウマチ科第50巻第2号 特集/感染症に伴う関節症の診断と治療解説制御性T細胞による免疫応答制御 大阪大学免疫学フロンティア研究センター実験免疫学 (2013)
  • Author(s): 濱口真英 坂口志文
  • Publisher: 科学評論社
• [Book] 標準免疫学第3版第7章 ホメオスタシス維持のメカニズム191-205 大阪大学免疫学フロンティア研究センター実験免疫学
  • Author(s): 執筆協力者 濱口真英
• [Remarks] 第1回肝臓と糖尿病・代謝研究会2014年7月4日 東京学術奨励賞受賞
• [Remarks] ライフサイエンス領域融合レビュー免疫系における恒常性の維持と制御性T細胞2013年5月15日 濱口真英・坂口志文 (大阪大学免疫学フロンティア研究センター実験免疫学)
  • URL: http://leading.lifesciencedb.jp/2-e005/
• [Remarks] 実験免疫学
  • URL: http://exp.immunol.ifrec.osaka-u.ac.jp/