• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Mechanisms of phenotypic changes in macrophages during tissue injury

Research Project

Project/Area Number 17H04068
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

TANAKA MASATO  東京薬科大学, 生命科学部, 教授 (00294059)

Co-Investigator(Kenkyū-buntansha) 大村谷 昌樹  兵庫医科大学, 医学部, 教授 (60398229)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Keywordsマクロファージ / 組織傷害 / 形質転換 / 単球 / 炎症 / 転写因子
Outline of Final Research Achievements

Macrophages play diverse roles in tissue injury. However, it remains unknown how these macrophages change phenotype according to each phase of tissue injury. This research aimed to reveal mechanisms of phenotypic changes in macrophages during tissue injury. As a result, we demonstrated that two transcriptional factors, c-Maf and Nrf2, determine the phenotype of CD169 macrophages during tissue injury. Furthermore, we identified a novel subpopulation of Ly6C-positive monocytes (Ym1- positive monocytes) in mice. Ym1-positive monocytes are generated in bone marrow during the phase of tissue repair, and contribute to resolution of inflammation and tissue repair in damaged tissues.

Academic Significance and Societal Importance of the Research Achievements

マクロファージは、組織傷害や炎症時に、外界の刺激や環境に素早く対応し、機能的、構造的な変化を起こすことが知られているが、その分子機構は不明な点が多かった。本研究の成果は、特定の転写因子がマクロファージの形質転換に分子スイッチとして働くことを明確に示しており、マクロファージの可塑性および組織傷害の病理を理解する上で有用な知見である。また、得られた知見は将来的に、炎症制御や組織修復促進を目的とした新たな疾患治療法の開発につながる可能性がある。

Report

(3 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report

Research Products

(19 results)

All 2019 2018 2017

All Journal Article Presentation Book

  • [Journal Article] Maea expressed by  macrophages, but not erythroblasts, maintains postnatal murine bone marrow erythroblastic islands.2019

    • Author(s)
      Wei Q, Boulais PE, Zhang D, Pinho S, Tanaka M, Frenette PS.
    • Journal Title

      Blood

      Volume: 133 Pages: 1222-1232

    • DOI

      10.1182/blood-2018-11-888180

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Macrophages Switch Their Phenotype by Regulating Maf Expression during Different Phases of Inflammation.2018

    • Author(s)
      Kikuchi Kenta、Iida Mayumi、Ikeda Naoki、Moriyama Shigetaka、Hamada Michito、Takahashi Satoru、Kitamura Hiroshi、Watanabe Takashi、Hasegawa Yoshinori、Hase Koji、Fukuhara Takeshi、Sato Hideyo、Kobayashi Eri H.、Suzuki Takafumi、Yamamoto Masayuki、Tanaka Masato、Asano Kenichi
    • Journal Title

      J Immunol

      Volume: 201 Pages: 635-51

    • DOI

      10.4049/jimmunol.1800040

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Emergence of immunoregulatory Ym1+Ly6Chi monocytes during recovery phase of tissue injury.2018

    • Author(s)
      Ikeda Naoki、Asano Kenichi、Kikuchi Kenta、Uchida Yoshimi、Ikegami Hiroki、Takagi Ryo、Yotsumoto Satoshi、Shibuya Takumi、Makino-Okamura Chieko、Fukuyama Hidehiro、Watanabe Takashi、Ohmuraya Masaki、Araki Kimi、Nishitai Gen、Tanaka Masato
    • Journal Title

      Sci Immunol.

      Volume: 3

    • DOI

      10.1126/sciimmunol.aat0207

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD169 macrophages regulate immune responses toward particulate materials in the circulating fluid.2018

    • Author(s)
      Deguchi Y, Nishina T, Asano K, Ohmuraya M, Nakagawa Y, Nakagata N, Sakuma T, Yamamoto T, Araki K, Mikami T, Tanaka M, Nakano H.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 505 Pages: 453-459

    • DOI

      10.1016/j.bbrc.2018.09.128

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD169 macrophages regulate immune responses toward particulate materials in the circulating fluid.2018

    • Author(s)
      Asano K, Kikuchi K, Tanaka M.
    • Journal Title

      J Biochem

      Volume: 164 Pages: 77-85

    • DOI

      10.1093/jb/mvy050

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tumor Necrosis Factor-Mediated Survival of CD169(+) Cells Promotes Immune Activation during Vesicular Stomatitis Virus Infection.2017

    • Author(s)
      Shinde PV, Xu HC, Maney SK, Kloetgen A, Namineni S, Zhuang Y, Honke N, Shaabani N, Bellora N, Doerrenberg M, Trilling M, Pozdeev VI, van Rooijen N, Scheu S, Pfeffer K, Crocker PR, Tanaka M, Duggimpudi S, Knolle P, Heikenwalder M, Ruland J, Mak TW, Brenner D, Pandyra AA, Hoell JI, Borkhardt A, Haussinger D, Lang KS
    • Journal Title

      J Virol

      Volume: 92 Pages: 01637-01637

    • DOI

      10.1128/jvi.01637-17

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hyperoxidation of ether-linked phospholipids accelerates neutrophil extracellular trap formation.2017

    • Author(s)
      Yotsumoto Satoshi、Muroi Yuito、Chiba Tatsuya、Ohmura Rio、Yoneyama Maki、Magarisawa Megumi、Dodo Kosuke、Terayama Naoki、Sodeoka Mikiko、Aoyagi Ryohei、Arita Makoto、Arakawa Satoko、Shimizu Shigeomi、Tanaka Masato
    • Journal Title

      Journal, Scientific Reports

      Volume: 7 Pages: 16026-16026

    • DOI

      10.1038/s41598-017-15668-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Macrophage Subset Expressing CD169 in Peritoneal Cavity-Regulated Mucosal Inflammation Together with Lower Levels of CCL22.2017

    • Author(s)
      Wang D, Li Q, Yang Y, Hao S, Han X, Song J, Yin Y, Li X, Tanaka M, Qiu CH.
    • Journal Title

      Inflammation

      Volume: 40 Pages: 1191-203

    • DOI

      10.1007/s10753-017-0562-0

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Depletion of myeloid cells exacerbates hepatitis and induces an aberrant increase in histone H3 in mouse serum2017

    • Author(s)
      Piao X, Yamazaki S, Komazawa-Sakon S, Miyake S, Nakabayashi O, Kurosawa T, Mikami T, Tanaka M, Van Rooijen N, Ohmuraya M, Oikawa A, Kojima Y, Kakuta S, Uchiyama Y, Tanaka M, Nakano H.
    • Journal Title

      Hepatology

      Volume: 65 Pages: 237-252

    • DOI

      10.1002/hep.28878

    • NAID

      120006528815

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] CD169+ macrophages orchestrate innate immune responses by regulating bacterial localization in the spleen.2017

    • Author(s)
      Perez OA, Yeung ST, Vera-Licona P, Romagnoli PA, Samji T, Ural BB, Maher L, Tanaka M, Khanna KM.
    • Journal Title

      Sci Immunol.

      Volume: 2 Pages: 1-12

    • DOI

      10.1126/sciimmunol.aah5520

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CD169 Expressing Macrophage, a Key Subset in Mesenteric Lymph Nodes Promotes Mucosal Inflammation in Dextran Sulfate Sodium-Induced Colitis.2017

    • Author(s)
      Li Q, Wang D, Hao S, Han X, Xia Y, Li X, Chen Y, Tanaka M, Qiu CH.
    • Journal Title

      Front Immunol

      Volume: 8 Pages: 669-669

    • DOI

      10.3389/fimmu.2017.00669

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CD11c+ resident macrophages drive hepatocyte death-triggered liver fibrosis in a murine model of nonalcoholic steatohepatitis.2017

    • Author(s)
      Itoh Michiko、Suganami Takayoshi、Kato Hideaki、Kanai Sayaka、Shirakawa Ibuki、Sakai Takeru、Goto Toshihiro、Asakawa Masahiro、Hidaka Isao、Sakugawa Hiroshi、Ohnishi Koji、Komohara Yoshihiro、Asano Kenichi、Sakaida Isao、Tanaka Masato、Ogawa Yoshihiro
    • Journal Title

      JCI insight

      Volume: 2 Pages: 1-16

    • DOI

      10.1172/jci.insight.92902

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Salt suppresses IFNgamma inducible chemokines through the IFNgamma-JAK1-STAT1 signaling pathway in proximal tubular cells.2017

    • Author(s)
      Arai Y, Takahashi D, Asano K, Tanaka M, Oda M, Ko SBH, Ko MSH, Mandai S, Nomura N, Rai T, Uchida S, Sohara E.
    • Journal Title

      Sci Rep

      Volume: 7 Pages: 46580-46580

    • DOI

      10.1038/srep46580

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Programmed cell death and the immune system.2017

    • Author(s)
      Nagata S, Tanaka M.
    • Journal Title

      Nat. Rev. Immunol.

      Volume: 17 Pages: 333-340

    • DOI

      10.1038/nri.2016.153

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] The role of immunoregulatory monocytes in the recovery phase of tissue injury2018

    • Author(s)
      田中正人
    • Organizer
      Australia-Japan Meeting on Cell Death
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Resolution of inflammation and tissue repair by immunoregulatory monocytes.2018

    • Author(s)
      田中正人
    • Organizer
      Cytokines2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ネトーシスと脂質酸化2017

    • Author(s)
      田中正人
    • Organizer
      第26回 日本Cell Death学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 酸化脂質によるneutrophil extracellular trap の形成2017

    • Author(s)
      田中正人
    • Organizer
      生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Book] Current Topics in Microbiology & Immunology, Vol.403  p.171-183 Immune Regulation by Dead Cell Clearance.2017

    • Author(s)
      S.Nagata & H.Nakano (eds.) Tanaka M, Nishitai G, et al.
    • Total Pages
      183
    • Publisher
      SPRINGER-VERLAG
    • ISBN
      9783319239125
    • Related Report
      2017 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi