腸管慢性炎症性腸疾患におけるTreg, Th17, Th17/Th1, Th1細胞の産生誘導, 競合性, 可塑性に関する総括的検討  [in Japanese] Development, Competition and Plasticity of the T-lymph cells in inflammatory bowel disease  [in Japanese]

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Author(s)

    • 金井 隆典 KANAI Takanori
    • 慶応義塾大学医学部消化器内科 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine

Abstract

  潰瘍性大腸炎およびクローン病に代表される炎症性腸疾患は,近年までCD4<sup>+</sup> Tリンパ球における'Th1/Th2サイトカインバランス'仮説に基づいて疾患が考えられてきた.近年,炎症を抑制する能力を持つ制御性T細胞,Th17細胞集団が登場し,最近ではIBDやIBDモデルを含むさまざまなヒト免疫疾患および動物モデルにおいて制御性T細胞の異常やTh17細胞の増加こそが真の病因ではないかと議論が広まっている.これまで,T細胞は最終的なeffector細胞になるとほかの細胞には変化しないとされていたが,T細胞間でも環境により表現型が変わることがわかり可塑性(Plasticity)という概念が構築されつつある.腸内細菌を含めた周辺の環境によりT細胞が誘導され,それぞれT細胞同士も周囲の環境によりPhenotypeを変えていることが判明しつつある.このような状況の中,炎症性腸疾患の原因が一つの因子でなく,多因子であり,T細胞の関与も複雑であることが判明してきている.これまで得られた結果をもとに炎症性腸疾患におけるT細胞の病態への関与についてT細胞の分化を踏まえて検討する.<br>

  The hypothesis of helper T (T(h))1/T(h)2 cytokine balance was often invoked to explain the development of inflammatory diseases, including inflammatory bowel diseases (IBD). Recently, a newly identified class of regulatory T cells (Tregs), which suppress inflammation and helper T(Th)17 cells, which produce Th17 family cytokines has been recognized as an essential subpopulation in the development of almost all kinds of human and animal inflammatory diseases. T cell subsets can act as terminally differentiated lineages, but they have been increasingly noted to demonstrated plasticity, depending on their surrounding such as intestinal microbiota. Th17 cells and Th1 cells coordinate to play a critical role in the formation of inflammatory bowel diseases. We showed Th1 and Th17 cells are competitive in lymphopenic mice, and that their orchestration results in a merged clinical phenotype of the two types of murine colitis. We also showed that Th17 and Th17/Th1 cells become colitogenic alternative Th1 cells via Th17, Th17/Th1, and Th1-like cells, independently of classical Th1 cells. Treg cells suppress this pathway, resulting in accumulation of Th17 and Th17/Th1 cells. Here we review T cell development including their plasticity and recent advances in the study of such Treg cells and Th17 cells in the pathogenesis of IBD.<br>

Journal

  • Japanese Journal of Clinical Immunology

    Japanese Journal of Clinical Immunology 35(5), 399-411, 2012-10-31

    The Japan Society for Clinical Immunology

References:  62

Codes

  • NII Article ID (NAID)
    10031130839
  • NII NACSIS-CAT ID (NCID)
    AN00357971
  • Text Lang
    JPN
  • Article Type
    ART
  • ISSN
    09114300
  • Data Source
    CJP  J-STAGE 
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