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The challenge for the development of therapy for autoimmune disorder by the establishment of artificial thymic medullary organ

Research Project

Project/Area Number 23659241
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionThe University of Tokushima

Principal Investigator

OHIGASHI Izumi  徳島大学, 疾患プロテオゲノム研究センター, 特任助教 (00596588)

Co-Investigator(Renkei-kenkyūsha) TAKAHAMA Yousuke  徳島大学, 疾患プロテオゲノム研究センター, 教授 (20183858)
NITTA Takeshi  徳島大学, 疾患プロテオゲノム研究センター, 講師 (30373343)
Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords免疫寛容 / 自己免疫 / 胸腺髄質上皮細胞 / 自己免疫寛容性
Research Abstract

As a step toward the establishment of an artificial thymic organ which could contribute to the treatment of autoimmune disease, the differentiation potential of thymic epithelial cells was examined. The objectives of this examination were to understand the molecular and cellular mechanisms underlying the separate development of the thymic cortical epithelial cell and thymic medullary epithelial cell lineages. We generated mice that express the recombinase Cre instead of β5t, a proteasome subunit that is abundant in thymic cortical epithelial cells and not detected in other cell types, including thymic medullary epithelial cells. By crossing β5t-Cre knock-in mice with loxP-dependent GFP reporter mice, we found that the vast majority of thymic medullary epithelial cells are differentiated fromβ5t-expressing progenitors. These results will help for the understanding of the nature of thymic microenvironment, and will give rational for the development of treatment for autoimmune disease.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (15 results)

All 2013 2012 2011 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (5 results)

  • [Journal Article] Aire-expressing thymic medullary epithelial cells originate from β5t-expressing progenitor cells2013

    • Author(s)
      Ohigashi I, Saulius Z, Sakata M (他6名)
    • Journal Title

      Proceedings of the National Academy of Sciences USA

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Development and function of cortical thymic epithelial cells2013

    • Author(s)
      Takada K, Ohigashi I (他3名)
    • Journal Title

      Current Topics Microbiology and Immunology

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lymphotoxin beta receptor regulates the development of CCL21-expressing subset of postnatal medullary thymic epithelial cells2013

    • Author(s)
      Lkhagvasuren E, Sakata M, Ohigashi I, Takahama Y.
    • Journal Title

      J Immunol

      Volume: 190 Issue: 10 Pages: 5110-5117

    • DOI

      10.4049/jimmunol.1203203

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The development of T lymphocytes in fetal thymus organ culture2013

    • Author(s)
      Nitta T, Ohigashi I, Takahama Y.
    • Journal Title

      Methods Mol Biol

      Volume: 946 Pages: 85-102

    • DOI

      10.1007/978-1-62703-128-8_6

    • ISBN
      9781627031271, 9781627031288
    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lymphotoxin b Receptor Regulates the Development of CC Chemokine Ligand Expressing Subset of Postnatal Medullary Thymic Epithelial Cells2013

    • Author(s)
      Enkhsaikhan Lkhagvasuren
    • Journal Title

      The Journal of Immunology

      Volume: 190

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thymic nurse cells provide microenvironment for secondary TCRα rearrangement in cortical thymocytes2012

    • Author(s)
      Nakagawa Y
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 109 Issue: 50 Pages: 20572-20577

    • DOI

      10.1073/pnas.1213069109

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rank signaling links the development of invariant γδ T cell progenitors and Aire+ medullary epithelium2012

    • Author(s)
      Roberts NM, White AJ, Jenkinson WE, Turchinovich G, Nakamura K, Withers DR, McConnell FM, Desanti GE, Benezech C, Parnell SM, Cunningham AF, Paolino M, Penninger J, Simon K, Nitta T, Ohigashi I, Takahama Y, Caamano JH, Hayday AC, Lane PJ, Jenkinson EJ, Anderson G
    • Journal Title

      Immunity

      Volume: 36 Issue: 3 Pages: 427-437

    • DOI

      10.1016/j.immuni.2012.01.016

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Thymic nurse cells provide microenvironment for secondary T cell receptor α rearrangement in cortical thymocytes.2012

    • Author(s)
      Nakagawa Y
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 109 Pages: 20572-20577

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rank signaling links the development of invariant γδ T cell progenitors and Aire(+) medullary epithelium.2012

    • Author(s)
      Roberts NA
    • Journal Title

      Immunity

      Volume: 36 Pages: 427-437

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of RANKL on the thymic medulla.2011

    • Author(s)
      大東いずみ
    • Journal Title

      European Journal of Immunology

      Volume: 41巻 Pages: 1822-1827

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Analysis of cortical and medullary bifurcation mechanisms in thymic epithelial cells using cortical thymic epithelial cell-specific β5t-Cre knock-in mice2012

    • Author(s)
      大東いずみ
    • Organizer
      第41回日本免疫学会総会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Year and Date
      2012-12-05
    • Related Report
      2012 Final Research Report
  • [Presentation] 胸腺皮質上皮細胞特異的β5t遺伝子座にCreをノックインしたマウスの作製2012

    • Author(s)
      大東いずみ
    • Organizer
      第22回Kyoto T cell conference
    • Place of Presentation
      和順会館(京都府)
    • Year and Date
      2012-07-06
    • Related Report
      2012 Final Research Report
  • [Presentation] 免疫不全を呈するヒトCD3eトランスジェニックマウス系統tge26におけるトランスジーン挿入部位の同定2011

    • Author(s)
      大東いずみ
    • Organizer
      日本免疫学会総会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Related Report
      2011 Research-status Report
  • [Presentation] Analysis of cortical and medullary bifurcation mechanisms in thymic epithelial cells using cortical thymic epithelial cell-specific β5t-Cre knock-in mice

    • Author(s)
      大東いずみ
    • Organizer
      日本免疫学会総会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 胸腺皮質上皮細胞特異的β5t遺伝子座にCreをノックインしたマウスの作製

    • Author(s)
      大東いずみ
    • Organizer
      Kyoto T cell Conference
    • Place of Presentation
      和順会館(京都府)
    • Related Report
      2012 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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