Epigallocatechin-3-Gallate Inhibits Expression of Receptors for T Cell Regulatory Cytokines and Their Downstream Signaling in Mouse CD4+ T Cells

Epigallocatechin-3-Gallate Inhibits Expression of Receptors for T Cell Regulatory Cytokines and Their Downstream Signaling in Mouse CD4+ T Cells

Author: Junpeng Wang, Munkyong Pae, Simin Nikbin Meydani and Dayong Wu

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.

 

Get the whole article here

Shipping Icon Free Shipping + Free Returns
Subscription Details Icon
We stand behind our teas and teaware, and want you to be not just satisfied with them, but thrilled. If for any reason you're not, just let us know and we'll do our best to make it right.

{property.value} {property.value} {property.value} Include jar: {property.value}
×
You definitely need tools!
Perfect coldbrew everytime
The ideal way to store your matcha
The ideal way to store your matcha