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United States Department of Agriculture

Agricultural Research Service

Research Project: NUTRITION, AGING, IMMUNE AND INFLAMMATORY RESPONSES IN HEALTH AND DISEASES

Location: Human Nutrition Research Center on Aging

Title: Epigallocatechin-3-gallate inhibits expression of receptors for T cell regulatory cytokines and their downstream signaling in mouse CD4+ T cells

Authors
item Wang, Junpeng -
item Pae, Munkyong -
item Meydani, Simin -
item Wu, Dayong S. -

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 21, 2011
Publication Date: February 23, 2012
Citation: Wang, J., Pae, M., Meydani, S.N., Wu, D. 2012. Epigallocatechin-3-gallate inhibits expression of receptors for T cell regulatory cytokines and their downstream signaling in mouse CD4+ T cells. Journal of Nutrition. 142:566-571.

Interpretive Summary: T cells, a type of white blood cell, are important to the immune system’s ability to defend itself from invading micro-organisms that cause disease and to defend the body from the growth of abnormal cells like cancers. They are also responsible for autoimmune disorders, which cause the body to attack itself, thus creating a number of conditions such as multiple sclerosis and rheumatoid arthritis. An important protein called interferon-2 (IL-2) is a key factor in T cell biology in the search to prevent autoimmune diseases from developing. Using nutrition to affect T cell function is a promising approach to improving immune system function or in suppressing the overactive response that causes autoimmune diseases. Green tea has components in them that are biologically active and can affect T cells. One such component is epigallocatechin gallate or EGCG, which inhibits T cell proliferation and function. In this study, we investigated the effect of EGCG on several protein molecules called IL-2, IL-7, and IL15. These are known to send signals to maintain and regulate T cell growth and functions. We found that EGCG interfered with the interaction between these molecules with their receptors, which are the structures on the cell surface that receive these molecules and relay the signals into the cells. This interference reduced the production and availability of T cells and therefore, EGCG can block the signal transmission and reduce the ability for T cells to become active as needed. The suppressive effect of EGCG on T cell growth cytokines suggests a potential nutritional strategy for suppressing T cells’ ability to over expand; therefore, this research suggests possible avenues for prevention and treatment of various autoimmune diseases.

Technical Abstract: We previously showed a suppressive effect of epigallocatechin-3-gallate (EGCG) on T cell cycling and expansion as well as a paradoxical effect on IL-2 levels (up-regulating) and IL-2 receptor (IL-2R)alpha expression (down-regulating). Thus, in the current study we tested the hypothesis that EGCG affects T cell responses via impairing the IL-2/IL-2R signaling. We found that EGCG inhibited anti-CD3/CD28-induced proliferation of naïve CD4+ T cells from C57BL/6 mice. EGCG increased accumulation of IL-2 but inhibited expression of IL-2R including all its subunits [IL-2R alpha, IL-2/IL-15R beta, common gamma chain (gamma-c)]. Using phosphorylation of STAT5 as a marker, we further found that EGCG suppressed IL-2R downstream signaling. Since IL-2R subunits IL-2/IL-15R beta- and gamma-c are shared with IL-15R and gamma-c is shared with IL-7R, we suspected that EGCG might also influence the signaling of IL-15 and IL-7, the two key regulators in maintaining T cell homeostasis. Results showed that EGCG suppressed IL-15 and IL-7 signaling; further, EGCG not only inhibited the subunits in IL-15R and IL-7R shared with IL-2R, but also affected their proprietary alpha chains in a manner that aligns with an impaired signaling. Although IL-2, IL-15, and IL-7 have separate and distinctive roles in regulating T cells, all of them are critical for T cell survival, expansion, and differentiation. Thus, these findings indicate an involvement of T cell growth cytokines in EGCG-induced T cell suppression through down-regulated expression of their receptors and downstream signaling. This implies a potential application in controlling dysregulated T cell functions such as those observed in autoimmune and inflammatory disorders.

Last Modified: 9/10/2014