Vaid Mudit, Prasad Ram, Singh Tripti, Katiyar Santosh K
Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA.
Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA.
Oncotarget. 2017 Jul 25;8(30):49625-49636. doi: 10.18632/oncotarget.17867.
Ultraviolet B (UVB) radiation induces regulatory T cells (Treg cells) and depletion of these Treg cells alleviates immunosuppression and inhibits photocarcinogenesis in mice. Here, we determined the effects of dietary grape seed proanthocyanidins (GSPs) on the development and activity of UVB-induced Treg cells. C3H/HeN mice fed a GSPs (0.5%, w/w)-supplemented or control diet were exposed to UVB (150 mJ/cm2) radiation, sensitized to 2,4-dinitrofluorobenzene (DNFB) and sacrificed 5 days later. FACS analysis indicated that dietary GSPs decrease the numbers of UVB-induced Treg cells. ELISA analysis of cultured sorted Treg cells indicated that secretion of immunosuppressive cytokines (interleukin-10, TGF-β) was significantly lower in Treg cells from GSPs-fed mice. Dietary GSPs also enhanced the ability of Treg cells from wild-type mice to stimulate production of IFNγ by T cells. These effects of dietary GSPs on Treg cell function were not found in XPA-deficient mice, which are incapable of repairing UVB-induced DNA damage. Adoptive transfer experiments revealed that naïve recipients that received Treg cells from GSPs-fed UVB-irradiated wild-type donors that had been sensitized to DNFB exhibited a significantly higher contact hypersensitivity (CHS) response to DNFB than mice that received Treg cells from UVB-exposed mice fed the control diet. There was no significant difference in the CHS response between mice that received Treg cells from UVB-irradiated XPA-deficient donors fed GSPs or the control diet. Furthermore, dietary GSPs significantly inhibited UVB-induced skin tumor development in wild-type mice but not in XPA-deficient mice. These results suggest that GSPs inactivate Treg cells by promoting DNA repair in dendritic cells in UVB-exposed skin.
紫外线B（UVB）辐射可诱导调节性T细胞（Treg细胞），而去除这些Treg细胞可减轻免疫抑制并抑制小鼠的光致癌作用。在此，我们确定了膳食葡萄籽原花青素（GSPs）对UVB诱导的Treg细胞的发育和活性的影响。给喂食GSPs（0.5%，w/w）补充饲料或对照饲料的C3H/HeN小鼠暴露于UVB（150 mJ/cm2）辐射下，使其对2,4-二硝基氟苯（DNFB）致敏，并在5天后处死。流式细胞术分析表明，膳食GSPs可减少UVB诱导的Treg细胞数量。对培养的分选Treg细胞进行酶联免疫吸附测定分析表明，来自喂食GSPs小鼠的Treg细胞中免疫抑制细胞因子（白细胞介素-10、转化生长因子-β）的分泌显著降低。膳食GSPs还增强了野生型小鼠Treg细胞刺激T细胞产生γ干扰素的能力。在无法修复UVB诱导的DNA损伤的XPA缺陷小鼠中未发现膳食GSPs对Treg细胞功能的这些影响。过继转移实验表明，接受来自喂食GSPs的经UVB照射的已对DNFB致敏的野生型供体的Treg细胞的未致敏受体，对DNFB的接触性超敏反应（CHS）明显高于接受来自喂食对照饲料的UVB暴露小鼠的Treg细胞的小鼠。接受来自喂食GSPs或对照饲料的经UVB照射的XPA缺陷供体的Treg细胞的小鼠之间的CHS反应没有显著差异。此外，膳食GSPs显著抑制野生型小鼠中UVB诱导的皮肤肿瘤发生，但对XPA缺陷小鼠无效。这些结果表明，GSPs通过促进UVB暴露皮肤中树突状细胞的DNA修复来使Treg细胞失活。
