Rheumatoid Arthritis

Arthritis and related conditions have been considered as the third largest contributor to direct health care expenditure, affecting nearly 46 million people in the USA. More important, the economic and social burden of arthritis is expected to grow, as the number of people with arthritis is expected to reach 67 million in the USA by 2030. Among various arthritis conditions, rheumatoid arthritis (RA) is the most common inflammatory arthritis worldwide. It is a chronic, progressive autoimmune disease characterized by cellular infiltration and proliferation of synovium, leading to progressive destruction of articular bone and cartilage. As RA tends to be progressive in nature, the current treatments, including conventional therapies and

Epigallocatechin-3-gallate (EGCG) is the most abundant and most biologically active catechin found in green tea. It is believed that EGCG possesses much of the health promoting properties of green tea, including anti-inflammatory, immunomodulatory and antioxidant effects. In 1999, Haqqi and colleagues first reported the disease modulating effects of green tea polyphenols (GTPs) on RA in a murine collagen-induced arthritis (CIA) model. They found the GTPs administration would significantly reduce the incidence and lower the disease severity of arthritis, associated with a marked reduction in the expression of IFN-γ, TNF-α, and cyclooxygenase(COX)-2, as well as total IgG and type II collagen-specific IgG (Ab) in arthritic joints. Later on, the therapeutic effects of green tea or EGCG have been consistently reported in series of experiments using either CIA or Adjuvant-induced arthritis (AIA) disease models. Interestingly, in a prospective cohort study with 31,336 subjects, Mikuls et al. reported that consuming tea >3 cups per day could significantly reduce the risk of RA

Of various T cells subsets, Regulatory T cells (Treg) play a vital role in maintaining immune tolerance and suppressing autoimmunity. Several studies demonstrated EGCG administration can increase the Treg cell frequency and number both in vitro and in vivo, accompanied with reduced T cell responses. However, how EGCG modulates Treg cells is unclear. The work from Carmen P et al. proposed that EGCG could function as DNA methyltransferase (DNMT) inhibitor to induce Foxp3 expression in naive CD4+ T cells, hence enhancing Treg cells via an epigenetic mechanism. Min et al. also found the increased frequency of Treg cells in the dLNs from EGCG-fed CIA mice. What’s new in their work is that they demonstrated a novel mechanism addressing how EGCG administration increases the number of Treg cells. First, they found EGCG could enhance IDO expression by CD11b+ DCs, and these CD11b+IDO+ DCs were functionally active. Second, using in vitro co-culture system, they reported that splenic CD11b+IDO+ DCs from EGCG-fed mice has more potent in differentiating CD4+CD25− T cells into Treg cells. Third, in order to answer whether these effects are IDO-dependent, an IDO inhibitor, 1-MT, was loaded into the CII antigen stimulated co-culture system.