|Wang, Junpeng - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Pae, Munkyong - Joslin Diabetes Center|
|Meydani, Simin - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Wu, Dayong - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
Submitted to: Journal of Molecular Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/28/2012
Publication Date: 3/30/2013
Citation: Wang, J., Pae, M., Meydani, S.N., Wu, D. 2013. Green tea epigallocatechin-3-gallate modulates differentiation of naive CD4+ T cells into specific lineage effector cells. Journal of Molecular Medicine. 91(4):485-495.
Interpretive Summary: Autoimmunity is an impaired response of the immune system in which the body attacks its own tissue as if it were harmful. Many conditions that occur such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease to name a few, are in fact autoimmune diseases. It is believed that various T cells, which are types of white cells important to the immune system, play an important role in the autoimmune response. CD4+ T helper (Th) cells are implicated in causing autoimmunity whereas regulatory T cells (Treg) seem to protect against the autoimmune response. Green tea and one of its components known as EGCG have been shown to improve symptoms associated with autoimmune inflammatory diseases in several animal models. One reason is that EGCG can alter the population of different types of T helper cells in the animal model of disease. In this study, we investigated how EGCG modifies the generation of various Th cells from a common precursor T cell (naïve T cells). We found that EGCG: reduced the development of the naïve T cells into Th cells that promote an autoimmune response, did not inhibit the development of Th2 cells that suppress the autoimmune response, and protected the positive response of the regulatory T cells, a type of T cell important in suppressing the autoimmune response. Our results suggest that EGCG controls the development of key T cells involved in regulating autoimmune diseases, which eventually leads to a diminished autoimmune response. These results will help us better understand how EGCG may favorably impact autoimmune diseases, which in turn may suggest uses for prevention of autoimmune diseases in humans.
Technical 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 previously showed that epigallocatechin-3-gallate (EGCG) attenuated experimental autoimmune encephalomyelitis (EAE) and altered 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 RORgamma-t, the specific transcription factors for Th1, Th9, and Th17 differentiation, respectively. These effects, in turn, may be mediated by EGCG-induced down-regulation 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.