Retinoic acid from retinal pigment epithelium induces T regulatory cells

被引:48
|
作者
Kawazoe, Yuko [1 ]
Sugita, Sunao [1 ]
Keino, Hiroshi [2 ]
Yamada, Yukiko [1 ]
Imai, Ayano [1 ]
Horie, Shintaro [1 ]
Mochizuki, Manabu [1 ]
机构
[1] Tokyo Med & Dent Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Bunkyo Ku, Tokyo 1138519, Japan
[2] Kyorin Univ, Sch Med, Dept Ophthalmol, Tokyo, Japan
关键词
retinal pigment epithelium; retinoic acid; T cells; TGF beta; immune privilege; GROWTH-FACTOR-BETA; TGF-BETA; BINDING-PROTEIN; VITAMIN-A; AUTOIMMUNE UVEORETINITIS; INFLAMMATORY CONDITIONS; IMMUNE PRIVILEGE; TH17; CELLS; FOXP3; DIFFERENTIATION;
D O I
10.1016/j.exer.2011.11.002
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
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.
引用
收藏
页码:32 / 40
页数:9
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