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Green tea epigallocatechin-3-gallate modulates differentiation of naïve CD4+ T cells into specific lineage effector cells

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Abstract

CD4+ T helper (Th) subsets Th1, Th9, and Th17 cells are implicated in inducing autoimmunity whereas regulatory T cells (Treg) have a protective effect. We and others have previously shown that epigallocatechin-3-gallate (EGCG) attenuates experimental autoimmune encephalomyelitis (EAE) and alters CD4+ T cell subpopulations. In this study, we investigated how EGCG impacts differentiation of naïve CD4+ T cells into different effector lineages and report that EGCG impeded Th1, Th9, and Th17 differentiation and prevented IL-6-induced suppression of Treg development. We further showed that EGCG inhibited T-bet, PU.1, and RORγt, the specific transcription factors for Th1, Th9, and Th17 differentiation, respectively. These effects, in turn, may be mediated by EGCG-induced downregulation of transducers p-STAT1 and p-STAT4 for Th1, and p-STAT3 for Th17. EGCG-induced change in Th17/Treg balance may be mediated by its inhibition of IL-6 signaling because EGCG inhibited soluble IL-6R, membrane gp130, and IL-6-induced phosphorylation of STAT3. This notion was further supported by the in vivo results showing inhibited IL-6 and soluble IL-6R but increased soluble gp130 levels in plasma from EAE mice fed EGCG. Together, our results suggest that EGCG modulates development of CD4+ T cell lineages through impacting their respective and interactive regulatory networks ultimately leading to an attenuated autoimmune response.

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Acknowledgments

The authors would like to thank Stephanie Marco for her help in the preparation of the manuscript. This work was supported by the USDA National Institute of Food and Agriculture (NIFA) grant #2010-65200-20360 and USDA, Agriculture Research Service contract #58-1950-0-014.

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The authors declare that they have no competing interests.

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  1. Munkyong Pae

    Present address: Cellular and Molecular Physiology Section, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02115, USA

Authors and Affiliations

  1. Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA, 02111, USA

    Junpeng Wang, Munkyong Pae, Simin Nikbin Meydani & Dayong Wu

  2. Department of Pathology, Sackler Graduate School of Biochemical Science, Tufts University, Boston, MA, 02111, USA

    Simin Nikbin Meydani

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  1. Junpeng Wang
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Correspondence to Dayong Wu.

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Supplemental Fig. 1

Effect of EGCG on Th2 differentiation. After naïve CD4+ T cells were cultured under polarized conditions in the presence of EGCG (10 μm). The percentage for IL-4 in CD4+ T cells was determined by FACS. A representative result of three independent experiments is shown (PPT 414 kb)

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Wang, J., Pae, M., Meydani, S.N. et al. Green tea epigallocatechin-3-gallate modulates differentiation of naïve CD4+ T cells into specific lineage effector cells. J Mol Med 91, 485–495 (2013). https://doi.org/10.1007/s00109-012-0964-2

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  • DOI: https://doi.org/10.1007/s00109-012-0964-2

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