Accumulation of functional regulatory T cells in actively inflamed liver in mouse dendritic cell-based autoimmune hepatic inflammation
Accumulation of functional regulatory T cells in actively inflamed liver in mouse dendritic cell-based autoimmune hepatic inflammation
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DOI：
10.1016/j.clim.2009.12.002
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发表时间：
2010-04-01
影响因子：
8.6
通讯作者：
Zeniya, Mikio
中科院分区：
文献类型：
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作者：
Saeki, Chisato;Nakano, Masanori;Zeniya, Mikio
使用新建立的基于树突状细胞（DC）的肝炎小鼠模型来检查THBE在自身免疫性肝脏炎症（AHI）的产生中的参与。AHI的炎症活性在DC疫苗接种后21天达到峰值。在第21天，叉头盒P3（Foxp 3）表达在肝脏中显著增加，但在脾脏中降低。第21天肝脏中的CD 4（+）CD 25（+）T细胞对CD 4（+）CD 25（+）T细胞的增殖具有抑制活性。在第21天，肝组织中TGFP上的CXCR 3及其配体CXCL 9的表达上调，并且肝脏中Treg分化所必需的转化生长因子（TGF）-β和IL-2的mRNA水平也增加。通过泼尼松龙治疗抑制AHI活性降低了肝脏中Treg的积累。通过CXCR 3/CXCL 9相互作用介导的Treg募集和通过上调的TGF-β和IL-2在肝脏中的扩增，可能发生Tcl 3的积累。(C)2009 Elsevier Inc. All rights reserved.
Participation of Tregs in the generation of autoimmune hepatic inflammation (AHI) was examined using a newly established dendritic cell (DC)-based mouse model of hepatitis. The inflammatory activity of AHI peaked 21 days after DC vaccination. Forkhead box P3 (Foxp3) expression on day 21 was significantly increased in the liver but was decreased in the spleen. CD4(+)CD25(+) Tregs from the liver on day 21 showed inhibitory activity against the proliferation of CD4(+)CD25(+) T cells. On day 21, the expression of CXCR3 on Tregs and its ligand CXCL9 in hepatic tissue was upregulated, and levels of mRNA of transforming growth factor (TGF)-beta and IL-2, essential for Treg differentiation, in the liver were also increased. Suppression of AHI activity by prednisolone treatment decreased Treg accumulation in the liver. Accumulation of Tregs might occur through Treg recruitment mediated by CXCR3/CXCL9 interaction and expansion in the liver by upregulated TGF-beta and IL-2. (C) 2009 Elsevier Inc. All rights reserved.