| First Author | Wang J | Year | 2012 |
| Journal | J Nutr | Volume | 142 |
| Issue | 3 | Pages | 566-71 |
| PubMed ID | 22323768 | Mgi Jnum | J:183267 |
| Mgi Id | MGI:5318150 | Doi | 10.3945/jn.111.154419 |
| Citation | Wang J, et al. (2012) Epigallocatechin-3-gallate inhibits expression of receptors for T cell regulatory cytokines and their downstream signaling in mouse CD4+ T cells. J Nutr 142(3):566-71 |
| abstractText | 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)alpha 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 naive CD4(+) T cells from C57BL/6 mice. EGCG increased accumulation of IL-2 but inhibited expression of IL-2R, including all its subunits [IL-2Ralpha, IL-2/IL-15Rbeta, and common gamma chain (gammac)]. Using phosphorylation of STAT5 as a marker, we further found that EGCG suppressed IL-2R downstream signaling. Because IL-2R subunits IL-2/IL-15Rbeta- and gammac are shared with IL-15R and gammac 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 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. |
