Curcumin induces the tolerogenic dendritic cell that promotes differentiation of intestine-protective regulatory T cells
Curcumin induces the tolerogenic dendritic cell that promotes differentiation of intestine-protective regulatory T cells
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DOI：
10.1002/eji.200939052
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发表时间：
2009-11-01
影响因子：
5.4
通讯作者：
Elson, Charles O.
中科院分区：
文献类型：
--
作者：
Cong, Yingzi;Wang, Lanfang;Elson, Charles O.
肠道是大量Treg的家园，正常小鼠肠道固有层中存在CD 4（+）CD 25（+）Treg和细菌抗原特异性Tr 1细胞。最近已经显示肠粘膜DC能够通过产生TGF-β和视黄酸（RA）诱导Foxp 3（+）Treg。然而，目前尚不清楚指示DC朝向这种粘膜表型的因素。姜黄素具有多种生物活性，包括抑制NF-κ B信号传导。我们想知道姜黄素是否可以调节DC成为耐受原，其功能可以模拟粘膜DC。我们在这里报告，姜黄素调制BM衍生的DC表达ALDH 1a和IL-10。这些姜黄素处理的DC诱导幼稚CD 4（+）T细胞分化为Treg，类似于肠道中的Treg，包括CD 4（+）CD 25（+）Foxp 3（+）Treg和产生IL-10的Tr 1细胞。这种Treg诱导需要由姜黄素调节的DC产生的IL-10、TGF-β和视黄酸。细胞接触以及IL-10和TGF-β的产生参与了这种诱导的Treg的功能。更重要的是，这些Treg在体外抑制抗原特异性T细胞活化，并在体内抑制由于抗原特异性病原性T细胞引起的结肠炎。
The gut is home to a large number of Treg, with both CD4(+) CD25(+) Treg and bacterial antigen-specific Tr1 cells present in normal mouse intestinal lamina propria. it has been shown recently that intestinal mucosal DC are able to induce Foxp3(+) Treg through production of TGF-beta plus retinoic acid (RA). However, the factors instructing DC toward this mucosal phenotype are currently unknown. Curcumin has been shown to possess a number of biologic activities including the inhibition of NF-kappa B signaling. We asked whether curcumin could modulate DC to be tolerogenic whose function could mimic mucosal DC. We report here that curcumin modulated BM-derived DC to express ALDH1a and IL-10. These curcumin-treated DC induced differentiation of naive CD4(+) T cells into Treg resembling Treg in the intestine, including both CD4(+)CD25(+) Foxp3(+) Treg and IL-10-producing Tr1 cells. Such Treg induction required IL-10, TGF-beta and retinoic acid produced by curcumin-modulated DC. Cell contact as well as IL-10 and TGF-beta production were involved in the function of such induced Treg. More importantly, these Treg inhibited antigen-specific T-cell activation in vitro and inhibited colitis due to antigen-specific pathogenic T cells in vivo.