Curcumin attenuates decline of CD69 expression on CD4+T cells and induces generation of CD25hiFoxp3+T cells through TGF-β1 production

Abstract

Curcumin is a promising candidate as a natural medicinal agent to treat chronic inflammatory diseases. However, little is known about curcumin-mediated CD4+ T cell regulation, which contributes to the therapeutic effects of curcumin. Here, we report that curcumin inhibits T-cell receptor (TCR)-triggered immune responses of CD4+ T cells through suppression of proliferation, cytokine production and differentiation of CD4+ T cells. Intriguingly, spontaneous decline of CD69 expression was attenuated by curcumin treatment, which continued until 6 days of culture. We showed that curcumin-mediated CD69 up-regulation was dependent on extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. Concomitantly, the expressions of C-C motif chemokine receptor 7 (CCR7), L-selectin and transforming growth factor-β1 (TGF-β1) were also increased. TGF-β1 production was moderate, but was high enough to lead to the late generation of CD25hiFoxp3+CD4+ T cells and to maintain prolonged suppression of CD4+ T cell activation. These findings suggest that the immunoregulatory role of curcumin is effective for CD4+ T cells.