Grape seed proanthocyanidin extract (GSPE) differentially regulates Foxp3(+) regulatory and IL-17(+) pathogenic T cell in autoimmune arthritis

作者：Park Mi Kyung; Park Jin Sil; Cho Mi La^*; Oh Hye Jwa; Heo Yu Jung; Woo Yun Ju; Heo Yang Mi; Park Min Jung; Park Hyun Sil; Park Sung Hwan; Kim Ho Youn; Min Jun Ki

来源：Immunology Letters, 2011, 135(1-2): 50-58.

DOI：10.1016/j.imlet.2010.09.011

• Grape seed proanthocyanidin extract (GSPE)
• Th17
• Foxp3
• Autoimmune arthritis
• Regulatory T cells
• Pathogenic T cells

Grape seed proanthocyanidin extract (GSPE), which is the antioxidant derived from grape seeds, has been reported to possess a variety of potent properties. We have previously shown that GSPE attenuates collagen-induced arthritis. However the mechanism by which GSPE regulates the immune response remains unclear, although it may involve effects on the regulation of pathogenic T cells in autoimmune arthritis. To clarify this issue, we have assessed the effects of GSPE on differential regulation of Th17 and regulatory T (Treg) cells subsets in vitro in mouse and human CD4(+) T cells. We observed that GSPE decreased the frequency of IL-17(+)CD4(+)Th17 cells and increased induction of CD4(+)CD25(+)forkhead box protein 3 (Foxp3)(+) Treg cells. In vivo, GSPE effectively attenuated clinical symptoms of established collagen-induced arthritis in mice with concomitant suppression of IL-17 production and enhancement of Foxp3 expression (type II collagen-reactive Treg cells) in CD4(+) T cells of joints and splenocytes. The presence of GSPE decreased the levels of IL-21, IL-22, IL-26 and IL-17 production by human CD4(+) T cells in a STAT3-dependent manner. In contrast, GSPE induces Foxp3(+). Treg cells in humans. Our results suggest that GSPE possesses a reciprocal control over IL-17 and Foxp3. By potently regulating inflammatory T cell differentiation, GSPE may serve as a possible novel therapeutic agent for inflammatory and autoimmune diseases, including rheumatoid arthritis.

• 出版日期2011-3-30
• 单位河北医科大学