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

Immunol Lett. 2011 Mar 30;135(1-2):50-8. doi: 10.1016/j.imlet.2010.09.011. Epub 2010 Oct 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / immunology
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Cytokines / immunology
  • Humans
  • Male
  • Mice
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Proanthocyanidins / chemistry
  • Proanthocyanidins / pharmacology*
  • Seeds / chemistry*
  • T-Lymphocytes, Regulatory
  • Th17 Cells
  • Vitis / chemistry*


  • Antioxidants
  • Cytokines
  • Plant Extracts
  • Proanthocyanidins
  • proanthocyanidin