|Wu, Dayong s.|
|Meydani, Simin n.|
Submitted to: Molecular Aspects of Medicine
Publication Type: Review article
Publication Acceptance Date: 10/14/2012
Publication Date: 1/15/2012
Citation: Wu, D., Wang, J., Pae, M., Meydani, S. 2012. Green tea EGCG, T cells, and T cell-mediated autoimmune diseases. Molecular Aspects of Medicine. 33:107-118. Interpretive Summary:
Technical Abstract: One of the proposed health benefits of consuming green tea is its protective effect on autoimmune diseases. Research on the immunopathogenesis of autoimmune diseases has made significant progression in the past few years and several key concepts have been revised. T cells, particularly CD4+ T helper (Th) cells, play a key role in mediating many aspects of autoimmune diseases. Upon antigenic stimulation, naïve CD4+ T cells proliferate and differentiate into different effector subsets. Th1 and Th17 cells are the pro-inflammatory subsets of Th cells responsible for inducing autoimmunity whereas regulatory T cells (Treg) have an antagonistic effect. Green tea and its active ingredient, epigallocatechin-3-gallate (EGCG), have been shown to improve symptoms and reduce the pathology in some animal models of autoimmune diseases. Whether or not EGCG’s effect is mediated through its impact on Th17 and Treg development has not been studied. We conducted a series of studies to investigate EGCG’s effect on CD4+ T cell proliferation and differentiation as well as its impact on the development of autoimmune disease. We first observed that EGCG inhibited CD4+ T cell expansion in response to either polyclonal or antigen specific stimulation. We then determined how EGCG affects naïve CD4+ T cell differentiation and found that it impeded Th1 and Th17 differentiation and prevented IL-6-induced inhibition on Treg development. We further demonstrated that EGCG inhibited Th1 and Th17 differentiation by downregulating their corresponding transcription factors (STAT1 and T-bet for Th1, and STAT3 and RORgamma t for Th17). These effects provide further explanation for previous findings that administration of EGCG by gavage to experimental autoimmune encephalomyelitis (EAE) mice, an animal model for human multiple sclerosis (MS), reduced the clinical symptoms, brain pathology, and proliferation and TNF-alpha production of encephalitogenic T cells. Upon further investigating the working mechanisms for EGCG’s protective effect in the EAE model, we showed that dietary EGCG dose-dependently attenuated the disease’s severity. This protective effect of EGCG is associated with the suppressed proliferation of autoreactive T cells, reduced production of pro-inflammatory cytokines, decreased Th1 and Th17, and increased Treg populations in lymphoid tissues and central nervous system. EGCG-induced shifts in CD4+ T cell subsets in EAE mice are accompanied by the corresponding changes in their regulator molecules. Recent studies have also highlighted the critical role of Th17/Treg balance in the pathogenesis of rheumatoid arthritis (RA). EGCG has been shown to be anti-inflammatory and protective in several studies using animal models of inflammatory arthritis, but research, at the best, only to start looking into the mechanisms with a focus on T cells. Overall, future research should fully incorporate the current progress in autoimmunity into the study design to expand the power of evaluating EGCG’s efficacy in treating autoimmune diseases. Data from human studies are essentially absent and thus are urgently needed.