Retinoic acid from retinal pigment epithelium induces T regulatory cells
Retinoic acid from retinal pigment epithelium induces T regulatory cells
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DOI：
10.1016/j.exer.2011.11.002
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发表时间：
2012-01-01
影响因子：
3.4
通讯作者：
Mochizuki, Manabu
中科院分区：
文献类型：
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作者：
Kawazoe, Yuko;Sugita, Sunao;Mochizuki, Manabu
原代培养的视网膜色素上皮细胞可通过包括转化生长因子β在内的抑制因子S在体外将T细胞转化为T调节细胞。维甲酸(RA)可增强转化生长因子β诱导的CD4(+)Tregs。我们研究了RPE细胞产生的RA是否能促进Tregs的生成。我们发现，在体外，RA处理的T细胞在重组转化生长因子β存在的情况下表达高水平的Foxp3。在基因芯片分析中，培养的RPE细胞结构性地表达RA相关分子，如RA结合蛋白、酶和受体。正常小鼠的RPE，但没有维生素A缺乏的小鼠，含有显著水平的转化生长因子β。RPE诱导的维生素A缺乏小鼠的Tregs未能抑制靶T细胞的激活。维生素A缺乏的实验性自身免疫性葡萄膜炎(EAU)小鼠眼内细胞中仅有少量Foxp3(+)T细胞，而正常EAU小鼠眼内细胞中Foxp3(+)T细胞的表达较高。RA受体拮抗剂处理或RA结合蛋白-siRNA转染的RPE细胞不能将CD4(+)T细胞转化为Tregs。我们的数据支持这样的假设，即RPE细胞产生RA，从而使旁观者T细胞通过转化生长因子β的促进作用转化为Tregs，然后Tregs可以参与眼睛免疫耐受的建立。(C)2011爱思唯尔有限公司。保留所有权利。
Primary cultured retinal pigment epithelial (RPE) cells can convert T cells into T regulatory cells (Tregs) through inhibitory factor(s) including transforming growth factor beta (TGF beta) in vitro. Retinoic acid (RA) enhances induction of CD4(+) Tregs in the presence of TGF beta. We investigated whether RA produced by RPE cells can promote generation of Tregs. We found that in vitro, RA-treated T cells expressed high levels of Foxp3 in the presence of recombinant TGF beta. In GeneChip analysis, cultured RPE cells constitutively expressed RA-associated molecules such as RA-binding proteins, enzymes, and receptors. RPE from normal mice, but not vitamin A-deficient mice, contained significant levels of TGF beta. RPE-induced Tregs from vitamin A-deficient mice failed to suppress activation of target T cells. Only a few Foxp3(+) T cells were found in intraocular cells from vitamin A-deficient experimental autoimmune uveitis (EAU) mice, whereas expression was higher in cells from normal EAU mice. RA receptor antagonist-pretreated or RA-binding protein-siRNA-transfected RPE cells failed to convert CD4(+) T cells into Tregs. Our data support the hypothesis that RPE cells produce RA, thereby enabling bystander T cells to be converted into Tregs through TGF beta promotion, which can then participate in the establishment of immune tolerance in the eye. (C) 2011 Elsevier Ltd. All rights reserved.