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Diagnosis and treatment of Langerhans cell histiocytosis by KIR2DL4

Research Project

Project/Area Number 16K19080
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Human pathology
Research InstitutionKyoto University

Principal Investigator

ueshima chiyuki  京都大学, 医学研究科, 技術職員 (80759449)

Research Collaborator Takei Yusuke  
Hirata Masahiro  
Sugimoto Akihiko  
Kurata Mariyo  
Moriyoshi Koki  
Haga Hironori  
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsKIR2DL4 / ヒトランゲルハンス細胞組織球症 / ERK / SHP-2 / ランゲルハンス細胞組織球症(LCH) / inhibitory receptor / ランゲルハンス細胞組織球症
Outline of Final Research Achievements

We examined the expression and function of KIR2DL4 in LCHs. In pathological specimens, 27 of 36 LCH cases (75.0%) were immunohistochemically positive for KIR2DL4. Its expression was independent of age, gender, location, multi-or single-system, and the status of BRAFV600E immunostaining. We also confirmed the expression of KIR2DL4 mRNA and protein in the human LCH-like cell lines ELD- 1 and PRU-1. KIR2DL4 protein was distributed in the membrane and cytoplasm of ELD-1 cells, but only in the cytoplasm of PRU-1 cells. An agonistic antibody against KIR2DL4 reduced phosphorylation of extracellular signal-regulated kinases (ERKs) and suppressed the cell growth of ELD-1 cells in a Src homology region 2 domain-containing phosphatase-2 dependent manner, but it had no effect in PRU-1 cells. These results suggest that KIR2DL4-mediated ERK suppression is a possible therapeutic target for LCH cells.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (6 results)

All 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (1 results)

  • [Journal Article] Killer cell immunoglobulin-like receptor 2DL4 is expressed in and suppresses the cell growth of Langerhans cell histiocytosis.2017

    • Author(s)
      Takei Y, Ueshima C, Kataoka TR, Hirata M, Sugimoto A, Rokutan-Kurata M, Moriyoshi K, Ono K, Murakami I, Iwamoto S, Haga H.
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 23 Pages: 36964-36972

    • DOI

      10.18632/oncotarget.16936

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CEACAM1 long isoform has opposite effects on the growth of human mastocytosis and medullary thyroid carcinoma cells.2017

    • Author(s)
      Chiyuki Ueshima, Tatsuki R. Kataoka, Yusuke Takei, Masahiro Hirata, Akihiko Sugimoto, Mitsuyoshi Hirokawa, Yoshimichi Okayama, Richard S. Blumberg, Hironori Haga.
    • Journal Title

      Cancer med.

      Volume: - Issue: 4 Pages: 845-856

    • DOI

      10.1002/cam4.1050

    • NAID

      120006309310

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Possible inducible skin-associated lymphoid tissues (iSALT)-like structures with CXCL13+ fibroblast-like cells in secondary syphilis2017

    • Author(s)
      Kogame T, Nomura T, Kataoka T, Hirata M, Ueshima C, Matsui M, Kabashima K
    • Journal Title

      Br J Dermatol

      Volume: in press Issue: 6 Pages: 1737-1739

    • DOI

      10.1111/bjd.15349

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A Case of Noonan Syndrome with Multiple Subcutaneous Tumours with MAPK-ERK/p38 Activation.2016

    • Author(s)
      Honda T, Kataoka TR, Ueshima C, Miyachi Y, Kabashima K.
    • Journal Title

      Acta Derm Venereol.

      Volume: 96 Pages: 130-131

    • NAID

      120006305918

    • Related Report
      2016 Research-status Report
  • [Journal Article] Clinical, Morphologic, and Pathologic Features Associated With Increased FDG Uptake in Schwannoma.2016

    • Author(s)
      Miyake KK, Nakamoto Y, Kataoka TR, Ueshima C, Higashi T, Terashima T, Nakatani K, Saga T, Minami S, Togashi K.
    • Journal Title

      AJR Am J Roentgenol.

      Volume: 207 Pages: 1288-1296

    • Related Report
      2016 Research-status Report
  • [Presentation] ヒトマスト細胞はKIR2DL4を発現し、妊娠成立に関与する2016

    • Author(s)
      上島 千幸、片岡 竜貴、平田 勝啓、南口 早智子、羽賀 博典、
    • Organizer
      第13回日本病理学会カンファレンス
    • Place of Presentation
      六甲山ホテル
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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