Abstract
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.
Highlights
It is well established that excessive exposure of the skin to solar ultraviolet (UV) radiation results in suppression of the immune system
To determine the effect of grape seed proanthocyanidins (GSPs) on the development of Treg cells, C3H/HeN mice fed a GSPs-supplemented diet or a control diet were exposed to Ultraviolet B (UVB) radiation and sensitized with DNFB as described in the Materials and Methods
As we have shown that GSPs inhibit UVB-induced immunosuppression by enhancing the repair of damaged DNA in UVB-exposed LC/dendritic cells (DCs) of the skin [27], we further checked the effect of GSPs on the numbers of Treg cells in xeroderma pigmentosum complementation group-A (XPA)-KO mice under identical experimental conditions
Summary
It is well established that excessive exposure of the skin to solar ultraviolet (UV) radiation results in suppression of the immune system. This UV-induced immunosuppression has been implicated in the UVinduced development of skin tumors. Chronically immunosuppressed patients who live in regions of intense sun exposure have an exceptionally high rate of non-melanoma skin cancer [1,2,3,4]. The association between immunosuppression and development of skin tumors is suggested by the high incidence of skin cancers, especially squamous cell carcinomas (SCCs), among organ transplant recipients who require prolonged immunosuppressive therapy [5,6,7,8]. Several lines of evidence indicated that www.impactjournals.com/oncotarget
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