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

ケモカインの情報伝達制御

Research Project

Project/Area Number 12051240
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKinki University

Principal Investigator

義江 修  近畿大学, 医学部, 教授 (10166910)

Co-Investigator(Kenkyū-buntansha) 野見山 尚之  熊本大学, 医学部, 講師 (00156225)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥78,300,000 (Direct Cost: ¥78,300,000)
Fiscal Year 2002: ¥26,400,000 (Direct Cost: ¥26,400,000)
Fiscal Year 2001: ¥27,000,000 (Direct Cost: ¥27,000,000)
Fiscal Year 2000: ¥24,900,000 (Direct Cost: ¥24,900,000)
Keywordsケモカイン / ケモカインレセプター / アトピー性皮膚炎 / 皮膚角化細胞 / 成人T細胞白血病 / Th2細胞 / EBウイルス / 細胞傷害性T細胞 / 炎症 / 免疫 / 喘息 / ノックアウトマウス / アトビー性皮膚炎
Research Abstract

本研究はケモカインによる情報伝達制御というテーマであるが、現時点では細胞内情報伝達の分子機構の解析よりも、むしろ細胞間でのケモカインを介する生理的および病的な細胞移動の解析が急務と考え、各種病態生理とケモカインの関係を中心に研究を行ってきた。今年度のおもな成果は以下の通りである。(1)CCR4は液性免疫やアレルギーに関与するTh2型メモリーT細胞や皮膚移行性メモリーT細胞に選択的に発現しているが、我々はアトピー性皮膚炎(AD)の患者ではCCR4のリガンドCCL17とCCL22の血漿中での値が有意に上昇し、病気の程度を表すSCORAD係数やEASI係数とよく相関すること、CCL17とCCL22はともに皮膚角化細胞をIFN-γで刺激すると産生されること、ADの患者ではさらに血小板中のCCL17値が上昇していること、などを明らかにし、CCR4系のAD病態形成での重要性を示した。(2)成人T細胞白血病(ATL)ではほとんど(>95%)の症例がCCR4陽性白血病であることを明らかにした。ATLの発生母地やATL細胞の性状(高率な皮膚浸潤性など)を理解し、さらにATLに対する新たな治療法を開発するうえで重要な知見である。(3)EBV形質転換B細胞でのケモカインレセプターの発現パターン(CCR6とCCR10の発現上昇とCXCR4とCXCR5の発現低下)を明らかにし、CCR6とCXCR4の変化はEBNA2やLMP1の作用であることを明らかにし、CCR10とCXCR5の変化はプラズマ細胞様の分化段階と関係を推測した。EBV形質転換細胞はリンパ組織では胚中心を避け、また粘膜下組織によく集まることをよく説明する。(4)CCR10の発現上昇とCXCR5の発現低下が実際にプラズマ細胞の分化形質であることを明らかにし、プラズマ細胞ではCCR10、CXCR4、CXCR6が選択的に発現することを明らかにした。また骨髄のストローマ細胞はこれらのレセプターに対するリガンド(CCL28、CXCL12、CXCL16)を高レベルで発現することを明らかにした。(5)CCR10のリガンドであるCCL28は唾液腺などの粘膜組織でのプラズマ細胞の組織内移入を誘導するとともに、粘膜上皮細胞から分泌され、強力な抗菌作用を発揮することを明らかにした。(6)CX3CR1はリンパ球の系統を問わず、パーフォリン陽性のキラー細胞に発現することを明らかにした。

Report

(3 results)
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Fujisawa, T., et al.: "Presence of high contents of thymus and activation-regulated chemokine in platelets and elevated plasma levels of thymus and activation-regulated chemokine and macrophage-derived chemokine in patients with atopic dermatitis"Journal of Allergy and Clinical Immunology. 110.1. 139-146 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshie, O., et al.: "Frequent expression of CCR4 in adult T-cell leukemia and human T-cell leukemia virus type 1-transformed T cells"Blood. 99・5. 1505-1511 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakayama, T., et al.: "Human B cells immortalized with Epstein-Barr virus upregulate CCR6 and CCR10 and downregulate CXCR4 and CXCR5"Journal of Virology. 76・6. 3072-3077 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nishimura, M., et al.: "Dual functions of fractalkine/CX3C ligand 1 in trafficking of perforin+/granzyme B+ cytotoxic effector lymphocytes that are defined by CX3CR1 expression"Journal of Immunology. 168・12. 6173-6180 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakayama, T., et al.: "Cutting edge : profile of chemokine receptor expression on human plasma cells account for their efficient recruitment to target tissues"Journal of Immunology. 170・3. 1136-1140 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hieshima, K., et al.: "CCL28 has dual roles in mucosal immunity as a chemokine with broad-spectrum antimicrobial activity"Journal of Immunology. 170・3. 1452-1461 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshie, O., et al.: "Chemokines in immunity"Advances in Immunology. 78. 57-110 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakayama, T., et al.: "Inducible expression of a CC chemokine liver and activation-regulated chemokine (LARC)/macrophage inflammatory protein (MIP)-3α/CCL2O by epidermal keratinocytes and its role in atopic dermatitis"International Immunology. 13・1. 95-103 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirai, H., et al.: "Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2"Journal of Experimental Medicine. 193・2. 255-261 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawasaki, S., et al.: "Intervention of thymus and activation-regulated chemokine attenuates the development of allergic airway inflammation and hyperresponsiveness in mice"Journal of Immunology. 166・3. 2055-2062 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirose, J., et al.: "Versican interacts with chemokines and modulates cellular responses"Journal of Biological Chemistry. 276・7. 5528-5534 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nomiyama, H., et al.: "Organization of the chemokine genes in the human and mouse major clusters of CC and CXC chemokines : diversification between the two species"Genes and Immunity. 2・2. 110-113 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Misu, T., et al.: "Chemokine receptor expression on T cells in blood and cerebrospinal fluid at relapse and remission of multiple sclerosis : imbalance of Th1/Th2-associated chemokine"J. Neuroimmunology. 114・1-114・2. 95-103 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Katou, F., et a!.: "Macrophage-derived chemokine (MDC/CCL22) and CCR4 are involved in the formation of T lymphocyte-dendritic cell clusters in human inflamed skin and secondary lymphoid tissue"American Journal of Pathology. 158・4. 1263-1270 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Patel, D.D., et al.: "Chemokines have diverse abilities to form solid phase gradients"Journal of Clinical Immunology. 99・1. 43-52 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iikura, M., et al.: "Chemokine receptors in human basophils : inducible expression of functional CXCR4"Journal of Leukocyte Biology. 70・1. 113-120 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nomiyama, H., et al.: "Human CC chemokine liver-expressed chemokine/CCL16 is a functional ligand for CCR1, CCR2 and CCR5, and constitutively expressed by hepatocytes"International Immunology. 13・8. 1021-1029 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miyamasu, M., et al.: "Variations in the human CC chemokine eotaxin gene"Genes and Immunity. 2・8. 461-463 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Terada, N., et al.: "The kinetics of allergen-induced eotaxin level in nasal lavage fluid : its key role in eosinophil recruitment in nasal mucosa"American Journal of Respiratory and Critical Care Medicine. 164・4. 575-579 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujiie, S., et al.: "Proinflammatory cytokines induce liver and activation-regulated chemokine/macrophage inflammatory protein-3α/CCL2O in mucosal epithelial cells through NF-κB"International Immunology. 13・10. 1255-1263 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Zlotnik,A.and Yoshie,O.: "Chemokines : a new classification system and their role in immunity"Immunity. 12・2. 121-127 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hasegawa,H., et al.: "Increased chemokine receptor CCR7/EBI1 expression enhances the infiltration of lymphoid organs by adult T-cell leukemia cells"Blood. 95・1. 30-38 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Goda,S., et al.: "CX3C-chemokine, fractalkine-enhanced adhesion of THP-1 cells to endothelial cells through integrin-dependent and -independent mechnisms"Journal of Immunology. 164・8. 4313-4320 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoneda,O., et al.: "Fractalkine-mediated endothelial cell injury by NK cells"Journal of Immunology. 164・8. 4055-4062 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sekiya,T., et al.: "Inducible expression of a Th2-type CC chemokine thymus and activation-regulated chemokine by human bronchial epithelial cells"Journal of Immunology. 165・4. 2205-2213 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakayama,T., et al.: "Inducible expression of a CC chemokine liver and activation-regulated chemokine (LARC)/macrophage inflammatory protein (MIP)-3alpha/CCL20 by epidermal keratinocytes and its role in atopic dermatitis"International Immunology. 13・1. 95-103 (2000)

    • Related Report
      2000 Annual Research Report

URL: 

Published: 2000-04-01   Modified: 2018-03-28  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi