| Summary: | 碩士 === 國立嘉義大學 === 微生物免疫與生物藥學系研究所 === 99 === Background：Alterations in immunity that occur with aging (immunosenescence) likely contribute to the development of autoimmune diseases. CD4＋CD25＋Foxp3＋ regulatory T cells (Treg) play an immunosuppressive role in immune system. They are responsible in the maintaining of immunological self-tolerance as well as immunohomeostasis. Age-associated increases in the population of Treg protect host against autoimmune diseases. Estrogen is known to increase Treg activity in facilitating immunological tolerance to fetal antigens. Stilbenes are known possessing phytoestrogenic activities. Among stilbene family, resveratrol is the most well-known and proved to have immunosuppressive activity by inhibiting T cell proliferation. In this study, we hypothesize that resveratrol and arachidin-1 might have exhibited a phytoestrogenic property to affect Treg cells development and their activity.
Result： Immunotoxicity of both resveratrol and arachidin-1 was assessed. There was no obvious cytotoxicity of resveratrol and arachidin-1 on immune cells when concentration was under 25 M and 5 M respectively. All experiments were therefore tested below the toxic concentrations. ConA stimulated lymphoblastogenesis of either spleen or thymus was inhibited by pre-treatment with resveratrol, arachidin-1 or E2. Flow cytometric analysis revealed that the peripheral Treg population was not altered by treatments, whereas Treg cell functions including CTLA-4, TGF-, and IL-10 were all upregulated by resveratrol, arachindin-1 and E2. And similar results were also demonstrated at mRNA level. Foxp3, the specific nuclear transcription factor of Treg , was also enhanced. The phytoestrogenic activity of resveratrol and arachidin-1 in inhibition of ConA induced lymphoblastogenesis was recovered by pre-treatment of estrogen receptor blocker, tamoxifen. In general, arachidin-1 and resveratrol showed limited effect on Treg population but greatly upregulate Treg activity. The immunomodulatory effect of stilbenes was further demonstrated in aged male ICR mice by a long term dietary supplementation of peanut sprout diet enriched with stilbenes. Dietary stilbenes enhanced Treg populations as well as stimulated mRNA expression of CTLA-4, TGF- and Foxp3 in enumerated purified Treg cells.
Conclusion： Aging resulted in immunosenescence and leading to autoimmune diseases, immunosuppressive Treg dominated conditions represented a successful aging. In this study, we demonstrated that peanut sprout enriched with stilbenes including resveratrol and arachidin-1 exhibited an estrogenic activity in upregualting Treg cell functions. Peanut sprouts diet enriched with stilbenes may have beneficial effects on aging individuals as a healthy supplement.
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