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J Nutr. 2012 Mar;142(3):566-71. doi: 10.3945/jn.111.154419. Epub 2012 Feb 8.

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

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  • 1Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.

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 (upregulating) and IL-2 receptor (IL-2R)α expression (downregulating). 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-2Rα, IL-2/IL-15Rβ, and common γ chain (γc)]. Using phosphorylation of STAT5 as a marker, we further found that EGCG suppressed IL-2R downstream signaling. Because IL-2R subunits IL-2/IL-15Rβ- and γc are shared with IL-15R and γc 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 α 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 downregulated 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.

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