Green tea EGCG, T cells, and T cell-mediated autoimmune diseases

Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, United States.
Molecular Aspects of Medicine (Impact Factor: 10.24). 02/2012; 33(1):107-18. DOI: 10.1016/j.mam.2011.10.001
Source: PubMed


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 RORγt 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-α 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.

Download full-text


Available from: Junpeng Wang, Oct 02, 2015
1 Follower
144 Reads
  • Source
    • "It is reported that grape seed proanthocyanidin extract could attenu- 186 ate collagen-induced arthritis (Cho et al. 2009), DNFB-induced contact 187 hypersensitivity and differentially regulate Foxp3 + regulatory and IL- 188 17 + pathogenic T cell in autoimmune arthritis (Park et al. 2011; Tang 189 et al. 2012). Epigallocatechin-3-gallate, the active ingredient of green 190 tea, has been shown to improve symptoms and reduce the pathology 191 in some T cell-mediated autoimmune diseases, including rheuma- 192 toid arthritis, multiple sclerosis, type 1 diabetes, inflammatory 193 bowel disease, Sjogren's syndrome, systemic lupus erythematosus, 194 and psoriasis (Wang et al. 2012; Wu et al. 2012). Proanthocyanidins' 195 anti-inflammatory mechanisms might be triggered by their antiox- 196 idant activities and regulation of multi-molecular, such as NF-κB, 197 mitogen-activated protein kinases, PI3K/Akt, caspases, cytokines, cell 198 cycle regulatory proteins and other check points, etc. (Nandakumar 199 et al. 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The leaves and bark of Metasequoia glyptostroboides are used as anti-microbic, analgesic and anti-inflammatory drug for dermatic diseases in Chinese folk medicine. However, the pharmacological effects and material basis responsible for the therapeutic use of this herb have not yet been well studied. The objectives of this study were to evaluate the anti-inflammatory effects of the proanthocyanidin fraction from the bark of M. glyptostroboides (MGEB) and to elucidate its immunological mechanisms. The anti-inflammatory activity of MGEB was evaluated using 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis (ACD) in mice. Its potential mechanisms were further investigated by determining its effects on Con A-induced T cell activation and Th1/Th17 responses in vitro. Both intraperitoneal injection and oral administration of MGEB significantly reduced the ear swelling in DNFB-induced ACD mice. MGEB inhibited Con A-induced proliferation and the expression levels of cell surface molecules CD69 and CD25 of T cells in vitro. MGEB also significantly decreased the production of Th1/Th17 specific cytokines (IL-2, IFN-γ and IL-17) and down-regulated their mRNA expression levels in activated T-cells. MGEB could ameliorate ACD, at least in part, through directly inhibiting T cells activation and Th1/Th17 responses. Copyright © 2015 Elsevier GmbH. All rights reserved.
    Phytomedicine 03/2015; 685(4). DOI:10.1016/j.phymed.2015.03.006 · 3.13 Impact Factor
  • Source
    • "Although the mechanism(s) by which nutraceuticals impact satellite cell function, including reducing pro-apoptotic targeting of satellite cells, is likely to be complex. Part of the improvement in apoptotic signaling in activated satellite cells may be due to an upregulation of antioxidants and a reduction of oxidative stress and/or inflammation after nutraceutical treatments including resveratrol (Jackson et al., 2010, 2011; Ryan et al., 2010) and green tea catechins (Ota et al., 2011; Wang et al., 2011; Andrade and Assuncao, 2012; Wu et al., 2012; Haramizu et al., 2013). Given the propensity for apoptosis to occur in satellite cells isolated from old hosts including humans (Fulle et al., 2012, 2013), further investigations into the potential for nutraceuticals to improve satellite cell function in aging are warranted. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The mechanisms contributing to sarcopenia include reduced satellite cell (myogenic stem cell) function that is impacted by the environment (niche) of these cells. Satellite cell function is affected by oxidative stress, which is elevated in aged muscles, and this along with changes in largely unknown systemic factors, likely contribute to the manner in which satellite cells respond to stressors such as exercise, disuse, or rehabilitation in sarcopenic muscles. Nutritional intervention provides one therapeutic strategy to improve the satellite cell niche and systemic factors, with the goal of improving satellite cell function in aging muscles. Although many elderly persons consume various nutraceuticals with the hope of improving health, most of these compounds have not been thoroughly tested, and the impacts that they might have on sarcopenia and satellite cell function are not clear. This review discusses data pertaining to the satellite cell responses and function in aging skeletal muscle, and the impact that three compounds: resveratrol, green tea catechins, and β-Hydroxy-β-methylbutyrate have on regulating satellite cell function and therefore contributing to reducing sarcopenia or improving muscle mass after disuse in aging. The data suggest that these nutraceutical compounds improve satellite cell function during rehabilitative loading in animal models of aging after disuse (i.e., muscle regeneration). While these compounds have not been rigorously tested in humans, the data from animal models of aging provide a strong basis for conducting additional focused work to determine if these or other nutraceuticals can offset the muscle losses, or improve regeneration in sarcopenic muscles of older humans via improving satellite cell function.
    Frontiers in Aging Neuroscience 09/2014; 6:246. DOI:10.3389/fnagi.2014.00246 · 4.00 Impact Factor
  • Source
    • "EGCG also displayed remarkably preventive effects on the chronic Available online at inflammatory diseases by inhibiting the activation of the endothelial cells and lymphocytes [11] [12] [13]. Several studies have revealed the neuroprotective effects of EGCG for neurodegenerative diseases, which were associated with its potential inhibitory effects on the activation of microglial cells [14], a kind of immune cells in the brain. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Infrasound, a kind of common environmental noise and a major contributor of vibroacoustic disease, can induce the central nervous system (CNS) damage. However, no relevant anti-infrasound drugs have been reported yet. Our recent studies have shown that infrasound resulted in excessive microglial activation rapidly and sequential inflammation, revealing a potential role of microglia in infrasound-induced CNS damage. Epigallocatechin gallate (EGCG), a major bioactive component in green tea, has the capacity of protecting against various neurodegenerative diseases via an anti-inflammatory mechanism. However, it's still unknown to date whether EGCG acts on infrasound-induced microglial activation and neuronal damage. We showed that, after 1-, 2- or 5-day exposure of rats to 16 Hz, 130 dB infrasound (2 h/day), EGCG significantly inhibited infrasound-induced microglial activation in rat hippocampal region, evidenced by reduced expressions of Iba-1 (a marker for microglia) and pro-inflammatory cytokines (IL-1β, IL-6, IL-18 and TNF-α). Moreover, infrasound-induced neuronal apoptosis in rat hippocampi was significantly suppressed by EGCG. EGCG also inhibited infrasound-induced activation of primary microglia in vitro and decreased the levels of pro-inflammatory cytokines in the supernatants of microglial culture, which were toxic to cultured neurons. Furthermore, EGCG attenuated infrasound-induced increases in nuclear NF-κB p65 and phosphorylated IκBα, and ameliorated infrasound-induced decrease in IκB in microglia. Therefore, our study provides the first evidence that EGCG acts against infrasound-induced neuronal impairment by inhibiting microglia-mediated inflammation through a potential NF-κB pathway-related mechanism, suggesting that EGCG can be used as a promising drug for the treatment of infrasound-induced CNS damage.
    The Journal of nutritional biochemistry 07/2014; 25(7). DOI:10.1016/j.jnutbio.2014.02.012 · 3.79 Impact Factor
Show more