Curcumin inhibits suppressive capacity of naturally occurring CD4+CD25+ regulatory T cells in mice in vitro

Accumulating evidence has demonstrated that naturally occurring CD4+CD25+ regulatory T cells (Tregs) are critical for maintenance of immunological tolerance and have been shown to be important in regulating the immune responses in many diseases. Curcumin, a phytochemical obtained from the rhizome of the plant Curcuma longa, has achieved the potential therapeutic interest to numerous immune-related disorders. However, the effect and mechanism of curcumin on Tregs remain largely elusive. In the present study, curcumin inhibition of the suppressive activity of CD4+CD25+ regulatory T cells appears to be dependent on three categories: inhibiting cell-cell contact by down-regulation of CTLA-4, suppressing inhibitory cytokine secretion and decreasing the ability to consume IL-2 and/or suppress IL-2 production. In addition, Foxp3 expression was also reduced on Tregs after curcumin stimulation. Moreover, we found that nuclear translocation of p65 and c-Rel, which is critical for Foxp3 and CD25 expressions, was markedly decreased in Tregs with curcumin stimulation. Based on the role of curcumin in the suppressive activity of Tregs, it may be feasible to use curcumin as an immunotherapy for Treg-related diseases, such as tumors and sepsis.

Graphical abstractDownload full-size imageHighlights► Treatment with Curcumin inhibits Treg‐induced proliferation defect and type 2 polarization of CD4+CD25‐T lymphocytes. ► Curcumin inhibited the suppressive activity of CD4+ CD25+ regulatory T cells appears to be dependent on three categories: inhibiting cell‐cell contact by down‐regulation of CTLA‐4 and Foxp3, suppressing inhibitory cytokine secretion and decreasing the ability to consume IL‐2 and/or suppress IL‐2 production. ► The nuclear translocation of p65 and c‐Rel, which are critical for Foxp3 and CD25 expression, was markedly decreased in Treg with Curcumin stimulation.