Identification of gene responsible for suppression of dendritic cells by regulatory T cells and their application to clinical immunotherapy

• Project/Area Number: 20599001
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Tohoku University
• Principal Investigator: ONISHI Yasushi Tohoku University, 病院, 助教 (10509574)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2008: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: 樹状細胞 / 制御性T細胞 / FoxO3a / Foxp3 / CTLA-4 / Foxo3a / 免疫寛容 / microRNA

Research Abstract

Regulatory T cells, lymphocytes suppressing immune reaction, highly express CTLA-4. CTLA-4 suppresses dendritic cells (DC), which maintains immune system in normal condition. It is known that FoxO3a is an essential molecule for DC suppression by CTLA-4 in a mouse model. However, Foxo3a knockdown in human DC resulted in the reduction of T cell proliferation. It is suggested that FoxO3a may augment immune reaction in human DC.

Research Products

• [Journal Article] Favorable Outcome of Unrelated Cord Blood Transplantation for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. (2011)
  • Author(s): Onishi Y, Sasaki O, Ichikawa S, Inokura K, Katsuoka Y, Ohba RO, Okitsu Y, Kohata K, Ohguchi H, Fukuhara N, Yokoyama H, Yamada MF, Yamamoto J, Ishizawa K, Kameoka J, Harigae H
  • Journal Title: Biol Blood Marrow Transplant. (in press.)
  • Peer Reviewed
• [Journal Article] Successful treatment with bortezomib and thalidomide for POEMS syndrome. (2011)
  • Author(s): Ohguchi H, Ohba R, Onishi Y, Fukuhara N, Okitsu Y, Yamamoto J, Ishizawa K, Ichinohasama R, Harigae H
  • Journal Title: Ann Hematol. (in press.)
  • Peer Reviewed
• [Journal Article] Favorable Outcome of Unrelated Cord Blood Transplantation for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (2011)
  • Author(s): Yasushi Onishi, 他15名
  • Journal Title: Biol Blood Marrow Transplant Volume: 未定(In press)
  • Peer Reviewed
• [Journal Article] Successful treatment with bortezomib and thalidomide for PO EMS syndrome (2011)
  • Author(s): Ohguchi H, Ohba R, Onishi Y, 他6名
  • Journal Title: Ann Hematol Volume: 未定(In press)
  • Peer Reviewed
• [Journal Article] Successful allogeneic hematopoietic stem cell transplantation for aggressive NK cell leukemia. (2010)
  • Author(s): Ichikawa S, Fukuhara N, Yamamoto J, Suzuki M, Nakajima S, Okitsu Y, Kohata K, Onishi Y, Ishizawa K, Kameoka J, Harigae H
  • Journal Title: Intern Med. 49 Pages: 1907-1910
  • NAID: 130000336874
  • Peer Reviewed
• [Journal Article] Pregnancy-associated thrombotic thrombocytopenic purpura with anti-centromere antibody-positive Raynaud's syndrome. (2010)
  • Author(s): Watanabe R, Shirai T, Tajima Y, Ohguchi H, Onishi Y, Fujii H, Takasawa N, Ishii T, Harigae H
  • Journal Title: Intern Med. 49 Pages: 1229-1232
  • NAID: 130000251661
  • Peer Reviewed
• [Journal Article] Allogeneic hematopoietic stem cell transplant following chemotherapy containing l-asparaginase as a promising treatment for patients with relapsed or refractory extranodal natural killer/T cell lymphoma, nasal type. (2010)
  • Author(s): Yokoyama H, Yamamoto J, Tohmiya Y, Yamada MF, Ohguchi H, Onishi Y, Okitsu Y, Fukuhara N, Ohba-Ohtsuka R, Kohata K, Ishizawa K, Kameoka J, Harigae H
  • Journal Title: Leuk Lymphoma. 51 Pages: 1509-1512
  • Peer Reviewed
• [Journal Article] Successful allogeneic hematopoietic stem cell transplantation for aggressive NK cell leukemia (2010)
  • Author(s): Ichikawa S, Fukuhara N, Yamamoto J, Suzuki M, Nakajima S, Okitsu Y, Kohata K, Onishi Y, 他3名
  • Journal Title: Intern Med Volume: 49 Pages: 1907-1910
  • NAID: 130000336874
  • Peer Reviewed
• [Journal Article] Plasma cell leukemia maintaining complete remission by syngeneic stem cell transplantation combined with low-dose thalidomide maintenance therapy. (2009)
  • Author(s): Abe M, Yokoyama H, Tohmiya Y, Okitsu Y, Ohguchi H, Kohata K, Yamamoto J, Onishi Y, Ishizawa K, Kameoka J, Harigae H
  • Journal Title: Intern Med. 48 Pages: 1833-1835
  • NAID: 130000122191
  • Peer Reviewed
• [Journal Article] Regulatory T cells : how do they suppress immune responses? (2009)
  • Author(s): Sakaguchi S, Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T
  • Journal Title: Int Immunol. 21 Pages: 1105-1111
  • NAID: 10027389567
  • Peer Reviewed
• [Journal Article] Acquired hemophilia A with sigmoid colon cancer : successful treatment with rituximab followed by sigmoidectomy. (2009)
  • Author(s): Ichikawa S, Kohata K, Okitsu Y, Suzuki M, Nakajima S, Yamada MF, Onishi Y, Yamamoto J, Suzuki S, Ishizawa K, Kameoka J, Harigae H
  • Journal Title: Int J Hematol. 90 Pages: 33-36
  • NAID: 10025162364
  • Peer Reviewed
• [Journal Article] A retrospective analysis of bortezomib therapy for Japanese patients with relapsed or refractory multiple myeloma : beta2-microglobulin associated with time to progression. (2009)
  • Author(s): Ohguchi H, Sugawara T, Ishikawa I, Okuda M, Tomiya Y, Yamamoto J, Onishi Y, Fujiwara Yamada M, Ishizawa K, Kameoka J, Harigae H
  • Journal Title: Int J Hematol. 89 Pages: 342-347
  • Peer Reviewed
• [Journal Article] Regulatory T cells : how do they suppress immune responses? (2009)
  • Author(s): Sakaguchi S, Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T.
  • Journal Title: Int Immunol. 21 Pages: 1105-1111
  • NAID: 10027389567
  • Peer Reviewed
• [Journal Article] A retrospective analysis of bortezomib therapy for Japanese patients with relapsed or refractory multiple myeloma : beta2-microglobulin associated with time to progression. (2009)
  • Author(s): Ohguchi H, Sugawara T, Ishikawa I, Okuda M, Tomiya Y, Yamamoto J, Onishi Y, 他4名
  • Journal Title: Int J Hematol. 89 Pages: 342-347
  • Peer Reviewed
• [Journal Article] CTLA-4 control over Foxp3^+ regulatory T cell function. (2008)
  • Author(s): Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, Fehervari Z, Nomura T, Sakaguchi S
  • Journal Title: Science 322 Pages: 271-275
  • Peer Reviewed
• [Journal Article] Foxp3^+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. (2008)
  • Author(s): Onishi Y, Fehervari Z, Yamaguchi T, Sakaguchi S.
  • Journal Title: Proc Natl Acad Sci USA. 105 Pages: 10113-10118
  • Peer Reviewed
• [Journal Article] CTLA-4 control over Foxp3^+ regulatory T cell function (2008)
  • Author(s): Wing K, Onishi Y et.al.
  • Journal Title: Science 322 Pages: 271-275
  • Peer Reviewed
• [Journal Article] Foxp3^+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation (2008)
  • Author(s): Onishi Y, Fehervari Z et.al.
  • Journal Title: Proc Natl Acad Sci USA 105 Pages: 10113-10118
  • Peer Reviewed
• [Journal Article] 制御性T細胞と樹状細胞のクロストーク (2008)
  • Author(s): 大西康, 坂口志文
  • Journal Title: 実験医学増刊樹状細胞による免疫制御と免疫制御と臨床応用 26 Pages: 3197-3203
• [Presentation] フルダラビン+大量エンドキサン+TBI 4Gyを前処置に用いた臍帯血移植の検討 (2011)
  • Author(s): 大西康、大場理恵、猪倉恭子、勝岡優奈、沖津庸子、木幡桂、福原規子、大口裕人、山本譲司、石澤賢一、張替秀郎
  • Organizer: 第33回日本造血細胞移植学会総会
  • Place of Presentation: 松山
  • Year and Date: 2011-03-10
• [Presentation] Allogeneic HSCT following imatinib/dasatinib for patients with CML in accelerated and blastic phase. (2010)
  • Author(s): Yasushi Onishi, Osamu Sasaki, Yuna Katsuoka, Masahiro Kobayashi, Mayumi Kamata, Rie Ohba, Yoko Okitsu, Katsura Kohata, Hiroto Ohguchi, Noriko Fukuhara, Hisayuki Yokoyama, Joji Yamamoto, Kenichi Ishizawa, Hideo Harigae
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-25
• [Presentation] Allogeneic HSCT following imatinib/dasatinib for patients with CML inaccelerated and blastic phase (2010)
  • Author(s): Yasushi Onishi, 他13名
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-25
• [Presentation] 進行期Extranodal NK/T cell lymphoma,nasal typeに対する同種造血幹細胞移植の有用性 (2010)
  • Author(s): 横山寿行,山本譲司,大口裕人,遠宮靖雄,大西康,鎌田真弓,渡辺龍,小林匡洋,沖津庸子,木幡桂,大場理恵,福原規子,山田実名美,石澤賢一,亀岡淳一,目黒邦昭,張替秀郎
  • Organizer: 第32回日本造血細胞移植学会総会
  • Place of Presentation: 浜松
  • Year and Date: 2010-02-20
• [Presentation] 自家末梢血幹細胞移植後再燃ホジキンリンパ腫に対してReduced-intensity Conditioningを用いて非血縁者間臍帯血移植を施行した一例 (2009)
  • Author(s): 大西康、鈴木真紀子、市川聡、中嶌真治、高橋太郎、沖津庸子、木幡桂、山本譲司、山田実名美、石澤賢一、亀岡淳一、張替秀郎
  • Organizer: 第31回日本造血幹細胞移植学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2009-02-05
• [Presentation] 東北大学グループで施行した寛解期Philadelphia染色体陽性急性リンパ性白血病に対する同種臍帯血移植成績-非血縁者間同種骨髄移植との比較 (2009)
  • Author(s): 市川聡、中嶌真治、鈴木真紀子、高橋太郎、井上あい、沖津庸子、木幡桂、藤原亨、福原規子、大西康、山本譲司、山田実名美、石澤賢一、佐々木治、遠宮靖雄、原崎頼子、奥田光崇、亀岡淳一、張替秀郎
  • Organizer: 第31回日本造血幹細胞移植学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2009-02-05
• [Presentation] Reduced-intensity Conditioningを用いて拒絶方向HLA血清学的二座不一致ドナーから末梢血幹細胞移植を施行した骨髄異形成症候群の一例 (2009)
  • Author(s): 鈴木真紀子、大西康、市川聡、中嶌真治、高橋太郎、沖津庸子、木幡桂、山本譲司、山田実名美、石澤賢一、亀岡淳一、張替秀郎
  • Organizer: 第31回日本造血幹細胞移植学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2009-02-05
• [Presentation] Prophylactic use of entecavir in a HBsAg-positive patient with MDS receiving unrelated BMT (2009)
  • Author(s): Yasushi Onishi, Satoshi Ichikawa, Shinji Nakajima, Makiko Suzuki, Yoko Okitsu, Katsura Kohata, Hiroto Oguchi, Noriko Fukuhara, Hisayuki Yokoyama, Jyoji Yamamoto, Kenichi Ishizawa, Hideo Harigae
  • Organizer: 第71 回日本血液学会学術集会
  • Place of Presentation: 京都
• [Presentation] 再発・難治性多発性骨髄腫に対するBortezomib療法の後方視的検討 (2008)
  • Author(s): 大口裕人,井根省二,阿部正理,大西康,石川泉,木幡桂,山本譲司,山田実名美,石澤賢一,遠宮靖雄,奥田光崇,菅原智広,亀岡淳一,張替秀郎
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-11
• [Presentation] 同種末梢血幹細胞移植施行7年後にドナー由来の再生不良性貧血を発症した1例 (2008)
  • Author(s): 高橋太郎、沖津庸子、大西康、鈴木真紀子、山本譲司、山田実名美、馬淵洋、松崎有未、亀岡淳一、張替秀郎
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-10
• [Book] 実験医学増刊(樹状細胞による免疫制御と免疫制御と臨床応用) (2008)
  • Author(s): 大西康,坂口志文
  • Publisher: 羊土社