title: Epigallocatechin-3-gallate ameliorates experimental autoimmune encephalomyelitis by altering balance among CD4+ T-cell subsets.
abstract: The green tea component epigallocatechin-3-gallate (EGCG) may be beneficial in autoimmune diseases; however, the underlying mechanisms are not well understood. In this study, we determined the effect of EGCG on the development of experimental autoimmune encephalomyelitis, 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% in diet) for 30 days and then immunized with specific antigen myelin oligodendrocyte glycoprotein 35-55. EGCG dose dependently attenuated clinical symptoms and pathological features (leukocyte infiltration and demyelination) in the central nervous system and inhibited antigen-specific T-cell proliferation and delayed-type hypersensitivity skin response. We further showed that EGCG reduced production of interferon-γ, IL-17, IL-6, IL-1β, and tumor necrosis factor-α; decreased types 1 and 17 helper T cells (Th1 and Th17, respectively); and increased regulatory T-cell populations in lymph nodes, the spleen, and the central nervous system. Moreover, EGCG inhibited expression of transcription factors T-box expressed in T cells and retinoid-related orphan receptor-γt, the specific transcription factor for Th1 and Th17 differentiation, respectively; the plasma levels of intercellular adhesion molecule 1; and CCR6 expression in CD4(+) T cells. These results indicate that EGCG may attenuate experimental autoimmune encephalomyelitis autoimmune response by inhibiting immune cell infiltration and modulating the balance among pro- and anti-autoimmune CD4(+) T-cell subsets. Thus, we identified a novel mechanism that underlies EGCG's beneficial effect in autoimmune disease.
authors: Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Sackler Graduate School of Biochemical Sciences, Tufts University, Boston, Massachusetts 02111, USA.
authors: Junpeng
authors: J
authors: Wang
authors: Zhihong
authors: Z
authors: Ren
authors: Yanmei
authors: Y
authors: Xu
authors: Sheng
authors: S
authors: Xiao
authors: Simin N
authors: SN
authors: Meydani
authors: Dayong
authors: D
authors: Wu
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003711:Demyelinating Diseases / Q000517:prevention & control; D019587:Dietary Supplements; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism; D009103:Multiple Sclerosis / Q000276:immunology / Q000517:prevention & control; D009185:Myelin Proteins / Q000037:antagonists & inhibitors; D063308:Myelin-Oligodendrocyte Glycoprotein; D009443:Neuritis / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000037:antagonists & inhibitors; D011897:Random Allocation; D020825:T-Box Domain Proteins / Q000037:antagonists & inhibitors; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D016207:Cytokines; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D018696:Neuroprotective Agents; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D002392:Catechin; C045651:epigallocatechin gallate