title: Green Tea Epigallocatechin-3-Gallate Suppresses Autoimmune Arthritis Through Indoleamine-2,3-Dioxygenase Expressing Dendritic Cells and the Nuclear Factor, Erythroid 2-Like 2 Antioxidant Pathway.
abstract: BACKGROUND
  The activity of one of the major catechins in Green Tea, the polyphenol (-)-epigallocatechin-3-gallate (EGCG), has been shown to have a variety of health benefits. Recent studies suggest that EGCG can modulate both the innate and adaptive arms of the immune system. The goal of the current studies was to examine the immunomodulatory effects and mechanisms of action of EGCG on experimental arthritis in mice.
  
  
  METHODS
  EGCG (10 mg/kg) was administered by oral gavage after CIA induction, while control mice were administered phosphate buffered saline (PBS). Disease mechanisms were studied in both groups of mice. Phenotypes were examined using repeated measure analysis of variance (ANOVA) and data from in vitro and ex vivo experiments were analyzed for significance using the Mann-Whitney U test.
  
  
  RESULTS
  EGCG treatment ameliorated clinical symptoms and reduced histological scores in arthritic mice. Serum type-II collagen-specific immunoglobulin (Ig) IgG2a antibodies were significantly lower in EGCG-fed mice compared to PBS-treated mice. EGCG significantly suppressed T cell proliferation and relative frequencies of CD4 T cells, CD8 T cells and B cell subsets including marginal zone B cells, T1 and T2 transitional B cells, while increasing the frequency of CD4(+) Foxp3(+) regulatory T cells (Tregs) and indoleamine-2,3-dioxygenase (IDO) expression by CD11b(+) dendritic cells (DC). Splenic CD11b(+) DC from EGCG fed mice induced an increased frequency of Tregs via an IDO-dependent mechanism in in vitro cultures. Importantly, joint homogenates from EGCG-fed mice exhibited significantly increased levels of Nuclear Factor, Erythroid 2-Like 2 (Nrf-2) and Heme oxygenase-1 (HO-1) compared with PBS-fed mice.
  
  
  CONCLUSIONS
  This is the first report of upregulation of the Nrf-2 antioxidant pathway in EGCG-mediated immunoregulation. EGCG ameliorated experimental arthritis in mice by eliciting IDO-producing DCs, increasing frequencies of T regs and inducing the activation of the Nrf-2 antioxidant pathway. It remains to be established whether EGCG is useful for the prevention and treatment of rheumatoid arthritis and other inflammatory disorders.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Bldg Y, Flr 8, Room 206 (Y8.206), Dallas, TX 75390-8884 USA.
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Min
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Bldg Y, Flr 8, Room 206 (Y8.206), Dallas, TX 75390-8884 USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Yan
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.
authors.forename: Sang Bum
authors.initials: SB
authors.lastname: Kim
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Bldg Y, Flr 8, Room 206 (Y8.206), Dallas, TX 75390-8884 USA.|Present address: Department of Biomedical Engineering, University of Houston, 3605 Cullen Blvd, Room 2027, Houston, TX 77204-5060 USA.
authors.forename: Sneha
authors.initials: S
authors.lastname: Ravikumar
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Bldg Y, Flr 8, Room 206 (Y8.206), Dallas, TX 75390-8884 USA.|Department of Internal Medicine, Rheumatism Center, Inha University School of Medicine, Incheon, South Korea.
authors.forename: Seong-Ryuel
authors.initials: SR
authors.lastname: Kwon
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Bldg Y, Flr 8, Room 206 (Y8.206), Dallas, TX 75390-8884 USA.|Present address: Department of Biomedical Engineering, University of Houston, 3605 Cullen Blvd, Room 2027, Houston, TX 77204-5060 USA.
authors.forename: Kamala
authors.initials: K
authors.lastname: Vanarsa
authors.affiliation: Department of Internal Medicine, Rheumatism Center, Inha University School of Medicine, Incheon, South Korea.
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Bldg Y, Flr 8, Room 206 (Y8.206), Dallas, TX 75390-8884 USA.
authors.forename: Laurie S
authors.initials: LS
authors.lastname: Davis
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Bldg Y, Flr 8, Room 206 (Y8.206), Dallas, TX 75390-8884 USA.|Present address: Department of Biomedical Engineering, University of Houston, 3605 Cullen Blvd, Room 2027, Houston, TX 77204-5060 USA.
authors.forename: Chandra
authors.initials: C
authors.lastname: Mohan
keywords: Collagen-induced arthritis; Green Tea (−)-epigallocatechin-3-gallate (EGCG); Nrf-2 signaling pathway; Regulatory T cells