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Reconstitution of mononuclear phagocyte system following allogeneic hematopoietic stem cell transplantation

Research Project

Project/Area Number 26461438
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionHokkaido University

Principal Investigator

Hashimoto Daigo  北海道大学, 大学病院, 講師 (20419576)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords同種造血幹細胞移植 / マクロファージ / 移植片対宿主病 / GVHD / 貪食細胞 / 造血幹細胞移植 / ステロイド / JAK1/2阻害剤 / 組織幹細胞 / 皮膚 / JAK阻害剤 / 腸管 / 腸内細菌叢
Outline of Final Research Achievements

Reconstitution of tissue resident macrophages and inflammatory macrophages after allogeneic hematopoietic stem cell transplantation (SCT) were assessed using murine model of allogeneic bone marrow transplantation (BMT). We found that severe GVHD promoted replacement of tissue resident macrophages in the target organs by donor-derived macrophages on day +14 after allogeneic BMT. Contrary, it took at least a few months for reconstitution of donor macrophages after syngeneic BMT, suggesting that allogeneic response accelerated donor reconstitution of tissue resident macrophages. Next, we addressed turnover of inflammatory macrophages after SCT. Massive infiltration of inflammatory macrophages was found in the lung and skin, and depletion of these cells using monoclonal antibodies ameliorated graft versus host disease (GVHD) after allogeneic SCT. Our findings have important clinical implications with respect to establishment of tolerance and pathophysiology of GVHD after allogeneic SCT.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (34 results)

All 2017 2016 2015 2014 Other

All Journal Article (18 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 17 results,  Acknowledgement Compliant: 3 results,  Open Access: 5 results) Presentation (12 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Risk factors of human herpesvirus 6 encephalitis/myelitis after allogeneic hematopoietic stem cell transplantation.2017

    • Author(s)
      Miyashita N, Endo T, Onozawa M, Hashimoto D, Kondo T, Fujimoto K, Kahata K, Sugita J, Goto H, Matsukawa T, Hashino S, Teshima T.
    • Journal Title

      Transpl Infect Dis.

      Volume: 印刷中 Issue: 3

    • DOI

      10.1111/tid.12682

    • NAID

      120006470980

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A leukemogenic kinase, FIP1L1-PDGFRA, and a SUMO E3 ligase, PIAS1, form a positive crosstalk via their enzymatic activities.2017

    • Author(s)
      M. Ibata, J. Iwasaki, Y. Fujioka, K. Nakagawa, S. Darmanin, M. Onozawa, D. Hashimoto, Y. Ohba, S. Hatakeyama, T. Teshima and T. Kondo.
    • Journal Title

      Cancer Sci.

      Volume: 108 Issue: 2 Pages: 200-207

    • DOI

      10.1111/cas.13129

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Graft-versus-host disease targets ovary and causes female infertility in mice.2017

    • Author(s)
      S. Shimoji, D. Hashimoto, H. Tsujigiwa, K. Miyawaki, K. Kato, S. Takahashi, R. Ogasawara, T. Jiromaru, H. Iwasaki, T. Miyamoto, K. Akashi, *T. Teshima
    • Journal Title

      Blood

      Volume: 129 Issue: 9 Pages: 1216-1225

    • DOI

      10.1182/blood-2016-07-728337

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MALDI-TOF MS in post-transplant bloodstream infections: reliable identification of causative bacteria in the neutropenic phase.2017

    • Author(s)
      Kanaya M, Hayashi Y, Hashimoto D, Endo T, Sugita J, Ohigashi H, Hashiguchi J, Matsukawa T, Matsuoka S, Kosugi-Kanaya M, Goto H, Onozawa M, Kahata K, Fujimoto K, Kondo T, Akizawa K, Shibuya H, Shimizu C, Teshima T.
    • Journal Title

      Bone Marrow Transplant.

      Volume: 印刷中 Issue: 5 Pages: 778-780

    • DOI

      10.1038/bmt.2016.365

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced-dose methotrexate in combination with tacrolimus was associated with rapid engraftment and recovery from oral mucositis without affecting the incidence of GVHD.2016

    • Author(s)
      Matsukawa T, Hashimoto D, Sugita J, Nakazawa S, Matsushita T, Kashiwazaki H, Goto H, Onozawa M, Kahata K, Fujimoto K, Endo T, Kondo T, Hashino S, Yamazaki Y, Teshima T.
    • Journal Title

      Int J Hematol.

      Volume: 104 Issue: 1 Pages: 117-124

    • DOI

      10.1007/s12185-016-1996-0

    • NAID

      120006313418

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expansion and Activation of CD103(+) Dendritic Cell Progenitors at the Tumor Site Enhances Tumor Responses to Therapeutic PD-L1 and BRAF Inhibition.2016

    • Author(s)
      Salmon H, Idoyaga J, Rahman A, Leboeuf M, Remark R, Jordan S, Casanova-Acebes M, Khudoynazarova M, Agudo J, Tung N, Chakarov S, Rivera C, Hogstad B, Bosenberg M, Hashimoto D, Gnjatic S, Bhardwaj N, Palucka AK, Brown BD, Brody J, Ginhoux F, Merad M.
    • Journal Title

      Immunity.

      Volume: 44 Issue: 4 Pages: 924-938

    • DOI

      10.1016/j.immuni.2016.03.012

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The Mononuclear Phagocyte System in Organ Transplantation.2016

    • Author(s)
      Ochando J, Kwan WH, Ginhoux F, Hutchinson JA, Hashimoto D, Collin M
    • Journal Title

      American Journal of Transplantation

      Volume: 16(4) Issue: 4 Pages: 1053-1069

    • DOI

      10.1111/ajt.13627

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cytogenetically Unrelated Clones in Acute Myeloid Leukemia Showing Different Responses to Chemotherapy.2016

    • Author(s)
      Kasahara K, Onozawa M, Miyashita N, Yokohata E, Yoshida M, Kanaya M, Kosugi-Kanaya M, Takemura R, Takahashi S, Sugita J, Shigematsu A, Takahata M, Fujisawa S, Hashimoto D, Fujimoto K, Endo T, Kondo T, Teshima T
    • Journal Title

      Case Rep Hematol.

      Volume: 2016 Pages: 1-5

    • DOI

      10.1155/2016/2373902

    • NAID

      120005822530

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Key players in intestinal GVHD2015

    • Author(s)
      橋本 大吾, 豊嶋 崇徳
    • Journal Title

      Rinsho Ketsueki

      Volume: 56 Issue: 7 Pages: 807-814

    • DOI

      10.11406/rinketsu.56.807

    • NAID

      130005093106

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Decreased secretion of Paneth cell α-defensins in graft-versus-host disease.2015

    • Author(s)
      Eriguchi Y, Nakamura K, Hashimoto D, Shimoda S, Shimono N, Akashi K, Ayabe T, Teshima T
    • Journal Title

      Transplant Infectious Disease

      Volume: 17 Issue: 5 Pages: 702-706

    • DOI

      10.1111/tid.12423

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice.2015

    • Author(s)
      Uryu H, Hashimoto D, Kato K, Hayase E, Matsuoka S, Ogasawara R, Takahashi S, Maeda Y, Iwasaki H, Miyamoto T, Saijo S, Iwakura Y, Hill GR, Akashi K, Teshima T.:
    • Journal Title

      Blood

      Volume: 125 Issue: 19 Pages: 3014-23

    • DOI

      10.1182/blood-2014-12-615781

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Requirement for Innate Immunity and CD90+ NK1.1- Lymphocytes to Treat Established Melanoma with Chemo-Immunotherapy.2015

    • Author(s)
      Moskalenko M, Pan M, Fu Y, de Moll EH, Hashimoto D, Mortha A, Leboeuf M, Jayaraman P, Bernardo S, Sikora AG, Wolchok J, Bhardwaj N, Merad M, Saenger Y
    • Journal Title

      Cancer Immunology Research

      Volume: 3 Issue: 3 Pages: 296-304

    • DOI

      10.1158/2326-6066.cir-14-0120

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning for mycosis fungoides and Sezary syndrome.2014

    • Author(s)
      Shiratori S, Fujimoto K, Nishimura M, Hatanaka KC, Kosugi-Kanaya M, Okada K, Sugita J, Shigematsu A, Hashimoto D, Endo T, Kondo T, Abe R, Hashino S, Matsuno Y, Shimizu H, Teshima T.
    • Journal Title

      Hematol Oncol

      Volume: Epub Ahead of Print Issue: 1 Pages: 9-16

    • DOI

      10.1002/hon.2162

    • NAID

      120005981361

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stenotrophomonas maltophilia infection during allogeneic hematopoietic stem cell transplantation: a single-center experience2014

    • Author(s)
      Shiratori S, Wakasa K, Okada K, Sugita J, Akizawa K, Shigematsu A, Hashimoto D, Fujimoto K, Endo T, Kondo T, Shimizu C, Hashino S, Teshima T
    • Journal Title

      Clin Transplant

      Volume: 28(6) Issue: 6 Pages: 656-661

    • DOI

      10.1111/ctr.12356

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Bone Marrow Graft-versus-Host Disease: Evaluation of Its Clinical Impact on Disrupted Hematopoiesis after Allogeneic Hematopoietic Stem Cell Transplantation2014

    • Author(s)
      Souichi Shiratori, Mizuha Kosugi-Kanaya, Satoshi Ueha, Junichi Sugita1, Akio Shigematsu, Takeshi Kondo, Daigo Hashimoto, Katsuya Fujimoto, Tomoyuki Endo, Mitsufumi Nishio, Satoshi Hashino, Yoshihiro Matsuno, Kouji Matsushima, Junji Tanaka, Masahiro Imamura, Takanori Teshima
    • Journal Title

      Biol Blood Marrow Transplant

      Volume: 20 Issue: 4 Pages: 495-500

    • DOI

      10.1016/j.bbmt.2013.12.568

    • NAID

      120005427744

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] FIP1L1 presence in FIP1L1-RARA or FIP1L1-PDGFRA differentially contributes to the pathogenesis of distinct types of leukemia2014

    • Author(s)
      Junko Iwasaki, Takeshi Kondo, Stephanie Darmanin, Makoto Ibata, Masahiro Onozawa, Daigo Hashimoto, Naoya Sakamoto and Takanori Teshima
    • Journal Title

      Annals of Hematology

      Volume: 未定 Issue: 9 Pages: 1473-1482

    • DOI

      10.1007/s00277-014-2085-1

    • NAID

      120005656326

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility.2014

    • Author(s)
      Muller PA, Koscso B, Rajani GM, Stevanovic K, Berres ML, Hashimoto D, Mortha A, Leboeuf M, Li XM, Mucida D, Stanley ER, Dahan S, Margolis KG, Gershon MD, Merad M, Bogunovic M
    • Journal Title

      Cell

      Volume: 158 Issue: 2 Pages: 300-313

    • DOI

      10.1016/j.cell.2014.04.050

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] マクロファージは末梢組織でも自己増殖する!?2014

    • Author(s)
      橋本大吾
    • Journal Title

      炎症と免疫

      Volume: 22 Pages: 411-415

    • Related Report
      2014 Research-status Report
  • [Presentation] Vitamin A-Coupled Liposomes Carrying siRNA Against HSP47 Ameliorate Skin Fibrosis in Chronic Graft-Versus-Host Disease2016

    • Author(s)
      Yamakawa T, Hashimoto D, Hayase E, Takahashi S, Teshima T
    • Organizer
      58th ASH Annual Meeting
    • Place of Presentation
      San Diego, USA, San Diego Convention Center
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] LGR5+ skin stem cells are targeted in GVHD and topical ruxolitinib protects them against GVHD2016

    • Author(s)
      高橋秀一郎, 橋本大吾, 早瀬英子, 豊嶋崇徳
    • Organizer
      第78回 日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2016-10-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] マクロファージ研究の最前線 (マクロファージの分化・維 持・可塑性に関して)2016

    • Author(s)
      橋本大吾
    • Organizer
      第26回日本樹状細胞研究会
    • Place of Presentation
      ホテル日航熊本 (熊本県熊本市)
    • Year and Date
      2016-09-02
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] R-spondin1 promotes Panted cell growth, maintains intestinal microbial ecology, and ameliorates GVHD.2016

    • Author(s)
      Hayase E, Hashimoto D, Nakamura K, Ogura Y, Hayashi T, Kurokawa K, Ayabe T, Teshima T.
    • Organizer
      The 7th JSH International Symposium
    • Place of Presentation
      淡路夢舞台国際会議場 (兵庫県淡路市)
    • Year and Date
      2016-05-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 急性 GVHD 予防における短期メトトレキセート投与量の検討2016

    • Author(s)
      松川 敏大, 杉田 純一, 中澤誠多朗, 阿部 貴恵, 柏崎 晴彦, 大東 寛幸, 金谷 穣, 後藤 秀樹, 小野澤真弘, 橋本大吾, 加畑馨, 藤本勝也, 遠藤知之, 近藤健, 山崎裕, 豊嶋崇徳
    • Organizer
      第38回日本造血細胞移植学会総会
    • Place of Presentation
      名古屋国際会議場 (名古屋市)
    • Year and Date
      2016-03-03
    • Related Report
      2015 Research-status Report
  • [Presentation] Topical ruxolitinib protects LGR5+ stem cells in the hair follicle and ameliorates skin graft- versus-host disease.2016

    • Author(s)
      Takahashi S, Hashimoto D, Hayase E, Teshima T
    • Organizer
      2016 BMT Tandem Meetings
    • Place of Presentation
      Hawaii Convention Center (Honolulu, USA)
    • Year and Date
      2016-02-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] R-spondin1 promotes Paneth cell growth, maintains intestinal microbial ecology, and ameliorates GvHD.2015

    • Author(s)
      Hayase E, Hashimoto D, Nakamura K, Ogura Y, Hayashi T, Kurokawa K, Ayabe T, Teshima T
    • Organizer
      57th ASH Annual Meeting
    • Place of Presentation
      Orange County Convention Center (Orlando, USA)
    • Year and Date
      2015-12-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Graft-Versus-Host Disease Targets Granulosa Cell of Ovarian Follicle and Causes Infertility after Allogeneic Hematopoietic Stem Cell Transplantation.2015

    • Author(s)
      Shimoji S, Hashimoto D, Kato K, Tujigiwa H, Akashi K, Teshima T
    • Organizer
      2015 BMT Tandem Meetings
    • Place of Presentation
      Manchester Grand Hyatt (San Diego, USA)
    • Year and Date
      2015-02-11 – 2015-02-15
    • Related Report
      2014 Research-status Report
  • [Presentation] Graft-Versus-Host Disease targets ovary and causes infertility after allo-HSCT2014

    • Author(s)
      Shimoji S, Kato K, Tujigiwa H, Eriguchi Y, Uryu H, Takashima S, Hashimoto D, Miyamoto T, Iwasaki H, Akashi K, Teshima T
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪国際会議場 (大阪市)
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Research-status Report
  • [Presentation] Key players in intestinal GVHD.2014

    • Author(s)
      Hashimoto D, Teshima T
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪国際会議場 (大阪市)
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] CSF-1/CSF-2による炎症性疾患制御2014

    • Author(s)
      橋本大吾, Arthur Mortha, 豊嶋崇徳, Miriam Merad
    • Organizer
      第79回日本インターフェロンサイトカイン学会学術集会
    • Place of Presentation
      北海道大学医学部学友会館フラテホール (札幌市)
    • Year and Date
      2014-06-19 – 2014-06-20
    • Related Report
      2014 Research-status Report
  • [Presentation] Tissue Resident Macrophages Self-maintain Locally Throughout Adult Life with Minimal Contribution from Circulating Monocytes.2014

    • Author(s)
      Hashimoto D
    • Organizer
      The 22nd International Symposium on Molecular Cell Biology of Macrophages
    • Place of Presentation
      神戸商工会議所 (神戸市)
    • Year and Date
      2014-06-02 – 2014-06-03
    • Related Report
      2014 Research-status Report
    • Invited
  • [Remarks] 橋本大吾オフィシャルウェブ

    • URL

      http://tenure-track.cris.hokudai.ac.jp/lab/hashimoto/

    • Related Report
      2015 Research-status Report 2014 Research-status Report
  • [Remarks] 北海道大学大学院医学研究科医学専攻内科学講座血液内科学分野

    • URL

      http://www.hokudai-hematology.jp/medical/results/

    • Related Report
      2015 Research-status Report
  • [Remarks] 北海道大学大学院 医学研究科医学専攻 内科学講座 血液内科学分野

    • URL

      http://www.hokudai-hematology.jp/medical/results/

    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] 皮膚線維症治療剤2015

    • Inventor(s)
      2015年5月29日
    • Industrial Property Rights Holder
      豊嶋崇徳, 橋本大吾, 新津洋司郎, 味呑憲二郎
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-05-29
    • Related Report
      2015 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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