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Title: Epigallocatechin-3-gallate ameliorates experimental autoimmune encephalomyelitis by altering balance among CD4+ T cell subsets

Author
item WANG, JUNPENG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item REN, ZHIHONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item XU, YANMEI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item XIAO, SHENG - Brigham & Women'S Hospital
item MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: American Journal of Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/14/2011
Publication Date: 1/15/2012
Citation: Wang, J., Ren, Z., Xu, Y., Xiao, S., Meydani, S.N., Wu, D. 2012. Epigallocatechin-3-gallate ameliorates experimental autoimmune encephalomyelitis by altering balance among CD4+ T cell subsets. American Journal of Pathology. 180:221-234.

Interpretive Summary: Studies suggest that green tea and one of its naturally occurring substances called epigallocatechin-3-gallate (EGCG) may benefit the treatment of autoimmune diseases. These are diseases in which the body’s immune system attacks its own tissues as non-self. Scientists would like to learn how this substance works in order to possibly make use of it in humans. In this study, they used an animal model known as EAE (experimental autoimmune encephalomyelitis), which duplicates a human autoimmune disease, multiple sclerosis, in order to learn the effect of EGCG on the development of EAE. The results showed that EGCG reduced the infiltration of disease-causing immune cells into the central nervous system and the tissue damage that would have occurred. Additionally we learned that EGCG was able to alter the composition and function of T cells. These results indicate that EGCG may reduce the development of EAE disease specifically be reducing production of important molecules that cause inflammation and autoimmune diseases and further, these findings could help design future clinical studies in order to use EGCG in reducing the burden of autoimmune diseases in humans.

Technical Abstract: Studies suggest that green tea component epigallocatechin-3-gallate (EGCG) may have a beneficial effect in reducing the pathogenesis of autoimmune diseases; however, the underlying mechanism(s) are not well understood. In this study, we determined the effect of EGCG on the development of experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis, and the underlying mechanisms. Female C57BL/6 mice were fed EGCG (0, 0.15, 0.3, and 0.6 percent in diet) for 30 d and then immunized with specific antigen MOG35-55. EGCG dose-dependently attenuated the clinical symptoms and pathology (leukocyte infiltration and demyelination) in the central nervous system (CNS) and inhibited antigen-specific T cell proliferation and delayed type hypersensitivity skin response. We further showed that EGCG reduced production of IFN-gamma, IL-17, IL-6, and TNF-alpha, decreased Th1 and Th17, and increased regulatory T cell populations in lymph nodes, spleen, and CNS. Moreover, EGCG inhibited expression of T-bet & RORgamma-t, the specific transcription factor for Th1 and Th17 differentiation, respectively, the plasma levels of adhesion moledule ICAM-1, and chemokine receptor CCR6 expression in CD4+ T cells. These results indicate that EGCG may attenuate EAE autoimmune response by inhibiting immune cell infiltration and by modulating the balance among pro-and anti-autoimmune CD4+ T cell subsets. Our findings support the proposed beneficial effect of EGCG in autoimmune disease and more importantly, we have identified a novel mechanism for this effect of EGCG.