樹状細胞-T細胞間における免疫修飾物質としてのドパミンの機能と関節リウマチの病態形成における役割  [in Japanese] Dopamine as an immune-modulator between dendritic cells and T cells and the role of dopamine in the pathogenesis of Rheumatoid Arthritis  [in Japanese]

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Author(s)

    • 中野 和久 NAKANO Kazuhisa
    • 産業医科大学医学部第一内科学講座 The first dept. of Internal Medicine, University of Occupational & Environmental Health
    • 松下 祥 MATSUSHITA Sho
    • 埼玉医科大学医学部免疫学 Department of Allergy and Immunology, Faculty of Medicine, Saitama Medical University
    • 齋藤 和義 SAITO Kazuyoshi
    • 産業医科大学医学部第一内科学講座 The first dept. of Internal Medicine, University of Occupational & Environmental Health
    • 山岡 邦宏 YAMAOKA Kunihiro
    • 産業医科大学医学部第一内科学講座 The first dept. of Internal Medicine, University of Occupational & Environmental Health
    • 田中 良哉 TANAKA Yoshiya
    • 産業医科大学医学部第一内科学講座 The first dept. of Internal Medicine, University of Occupational & Environmental Health

Abstract

  ドパミンD2様受容体の過剰反応が主原因とされる統合失調症においては,関節リウマチ(RA)の発症率が顕著に低下することが知られるが,その原因は不詳である.神経伝達物質はリンパ球表面の受容体を介して免疫修飾作用を発揮する.脳内の主要な神経伝達物質であるドパミンは,D1~D5のサブタイプを持つ7回膜貫通型のGPCRを介してシグナルを転送する.<br>   我々はこれまでに樹状細胞(DC)でのドパミン合成・貯蔵とナイーブT細胞への放出機構,およびヘルパーT細胞サブセット分化への影響を解明した.RAにおいてもDCは関節内抗原をT細胞に提示し病態形成の初期から重要な役割を果たすことから,RA滑膜組織におけるドパミン・ドパミン受容体の機能的役割を評価した.本稿ではこの一連の解析を概説し,ドパミン受容体を標的とした創薬の可能性についても述べる.<br>

  The nerve systems affect immune functions by releasing neurotransmitters through lymphocyte cell-surface receptors. A major neurotransmitter dopamine transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. There is wide evidence for a decreased risk of rheumatoid arthritis (RA) in patients with schizophrenia which is associated with the excessive stimulation of D2-like receptors by dopamine. However, the reason for the negative association between RA and schizophrenia is unknown.<br>   We previously demonstrated that dendritic cells (DCs) could synthesize and store dopamine, DC released dopamine to naive CD4 T cells upon DC-T cell interaction and affected helper T-cell differentiation. Because DCs have been proposed to play a pivotal role in the initiation and perpetuation of RA by presentation of arthritogenic antigens to T cells, we here assessed effects and functions of dopamine on immune cells during the pathogenesis of RA.<br>   In this paper, we overview the series of our research findings, and present the possibility of drug discovery which target at dopamine receptors.<br>

Journal

  • Japanese Journal of Clinical Immunology

    Japanese Journal of Clinical Immunology 32(1), 1-6, 2009-02-28

    The Japan Society for Clinical Immunology

References:  16

Codes

  • NII Article ID (NAID)
    10024961683
  • NII NACSIS-CAT ID (NCID)
    AN00357971
  • Text Lang
    JPN
  • Article Type
    REV
  • ISSN
    09114300
  • Data Source
    CJP  J-STAGE 
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