A conditioning machinery of dendritic cells by epithelial cells in the gut

• Project/Area Number: 25460586
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Hoshi University (2015); Tokyo Medical and Dental University (2013-2014)
• Principal Investigator: TEZUKA HIROYUKI 星薬科大学, 先端生命科学研究センター, 特任准教授 (30375258)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腸管上皮細胞 / 樹状細胞 / TGF-β / IgA / 免疫寛容 / TGF-beta

Outline of Final Research Achievements

Gut dendritic cells (DC) are distinct from peripheral lymph node DC in terms of their phenotypes and functions. We found that TGF-b, which is an abundant cytokine in the gut, is essential for the conditioning of DC in the gut. We generated conditional knockout mice with DC-specific deletion of type II TGF-b receptor (TbRII-DCKO), and found that TbRII-DCKO mice develop spontaneously autoimmune-like diseases, which are characterized by inflammatory cell migration into several organs and autoantibody production. Interestingly, in TbRII-DCKO mice that had developed the diseases, some commensal bacteria were detected in peripheral lymphoid organs, and the symptom and host survival were partly improved by treatment with antibiotics.

Research Products

• [Journal Article] Cytosine-phosphorothionate- guanine oligodeoxynucleotides exacerbates hemophagocytosis by inducing tumor necrosis factor-α production in mice after bone marrow transplanation. (2016)
  • Author(s): Liu J, Guo YM, Onai N, Ohyagi H, Hirokawa M, Takahashi N, Tagawa H, Ubukawa K, Kobayahi I, Tezuka H, Minamiya Y, Ohteki T, and Sawada K.
  • Journal Title: Biol Blood Marrow Transplant 2015 Volume: 印刷中 Issue: 4 Pages: 627-636
  • DOI: 10.1016/j.bbmt.2015.12.018
  • Peer Reviewed / Open Access
• [Journal Article] Immunomodulatory effects of soybeans and processed soy food compounds. (2015)
  • Author(s): Hiroyuki Tezuka, and Shinjiro Imai.
  • Journal Title: Recent Patents on Food, Nutrition and Agriculture Volume: 7 Pages: 92-99
  • Peer Reviewed
• [Journal Article] IgA生産を制御する樹状細胞サブセット (2014)
  • Author(s): 手塚裕之、安部由紀子、黒田聖子、樗木俊聡
  • Journal Title: 臨床免疫・アレルギー科 Volume: 62 Pages: 593-599
• [Journal Article] CXCL10-CXCR3 enhances the development of neutrophil-mediated fulminant lung injury of viral and nonviral origin. (2013)
  • Author(s): Ichikawa, A., Kuba, K., Morita, M., Chida, S., Tezuka, H.
  • Journal Title: Am. J. Respir. Crit.Care Med. Volume: 187 Issue: 1 Pages: 65-77
  • DOI: 10.1164/rccm.201203-0508oc
  • Peer Reviewed
• [Presentation] TLR9 signaling exerts HPS in BMT mice and is effectively treated through TNF-α inhibition (2015)
  • Author(s): 劉嘉嘉, 郭永梅, 大八木秀明, 広川誠, 高橋直人, 鵜生川久美, 小林五十鈴, 南谷佳弘, 手塚裕之, 小内伸幸, 樗木俊聡, 澤田賢一
  • Organizer: 日本血液学会学術集会
  • Place of Presentation: ホテル日航金沢
  • Year and Date: 2015-10-16
• [Presentation] Autophagy-dependent regulation of intestinal homeostasis by dendritic cells (2014)
  • Author(s): Hiroyuki Tezuka, Toshiaki Ohteki
  • Organizer: 日本免疫学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] TNF/iNOS-producing dendritic cells are originated from inflammatory monocytes and regulate gut IgA production. (2013)
  • Author(s): Tezuka, H., and Ohteki, T.
  • Organizer: 第42回 日本免疫学会総会 学術集会記録
  • Place of Presentation: 幕張メッセ
• [Remarks] 東京医科歯科大学難治疾患研究所生体防御学分野
  • URL: http://www.tmd.ac.jp/mri/bre/index.html
• [Remarks] 東京医科歯科大学 難治疾患研究所 生体防御学分野
  • URL: http://www.tmd.ac.jp/mri/bre/index.html