トキタ ダイスケ   TOKITA Daisuke
  時田 大輔
   所属   医学部 医学科(東京女子医科大学病院)
   職種   教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Poor allostimulatory function of liver plasmacytoid DC is associated with pro-apoptotic activity, dependent on regulatory T cells.
掲載誌名 正式名:Journal of hepatology
略  称:J Hepatol
ISSNコード:01688278/01688278
掲載区分国外
巻・号・頁 49(6),pp.1008-18
著者・共著者 Tokita Daisuke, Sumpter Tina L, Raimondi Giorgio, Zahorchak Alan F, Wang Zhiliang, Nakao Atsunori, Mazariegos George V, Abe Masanori, Thomson Angus W
担当区分 筆頭著者
発行年月 2008/12
概要 BACKGROUND/AIMS:The liver is comparatively rich in plasmacytoid (p) dendritic cells (DC), - innate immune effector cells that are also thought to play key roles in the induction and regulation of adaptive immunity.METHODS:Liver and spleen pDC were purified from fms-like tyrosine kinase ligand-treated control or lipopolysaccharide-injected C57BL/10 mice. Flow cytometric and molecular biologic assays were used to characterize their function and interaction with naturally occurring regulatory T cells (Treg).RESULTS:While IL-10 production was greater for freshly isolated liver compared with splenic pDC, the former produced less bioactive IL-12p70. Moreover, liver pDC expressed a low Delta4/Jagged1 Notch ligand ratio, skewed towards T helper 2 cell differentiation/cytokine production, and promoted allogeneic CD4(+)T cell apoptosis. T cell proliferation in response to liver pDC was, however, enhanced by blocking IL-10 function at the initiation of cultures. In the absence of naturally occurring CD4(+)CD25(+) regulatory T cells, similar levels of T cell proliferation were induced by liver and spleen pDC and the pro-apoptotic activity of liver pDC was reversed.CONCLUSIONS:The inferior T cell allostimulatory activity of in vivo-stimulated liver pDC may depend on the presence and function of Treg, a property that may contribute to inherent liver tolerogenicity.
DOI 10.1016/j.jhep.2008.07.028
PMID 18926588