Immunological benefits by ginseng through reciprocal regulation of th17 and treg cells during cyclosporine-induced immunosuppression

Background: It is not clear whether ginseng affects cyclosporine A (CsA)-induced desirable immunosuppressive action. In this study, we evaluated the immunological influence of combined treatment of ginseng with CsA. Methods: Using CD4þ T cells from mouse spleens stimulated with the T cell receptor (TCR) or allogeneic antigen-presenting cells (APCs), we examined the differentiation of naïve T cells into T helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs), and their cytokine production during treatment by Korean Red Ginseng extract (KRGE) and/or CsA. The influence of KRGE on the allogeneic T cell response was evaluated by mixed lymphocyte reaction (MLR). We also evaluated whether signal transducer and activator of transcription 3 (STAT3) and STAT5 are implicated in this regulation. Results: Under TCR stimulation, KRGE treatment did not affect the population of CD4þinterferon gamma (IFNg)þ and CD4þinterleukin (IL)-4þ cells and their cytokine production compared with CsA alone. Under the Th17-polarizing condition, KRGE significantly reduced the number of CD4þIL-17þ cells and CD4þ/phosphorylated STAT3 (p-STAT3)þ cells, but increased the number of CD4þCD25þforkhead box P3 (Foxp3)þ cells and CD4þ/p-STAT5þ cells compared with CsA alone. In allogeneic APCs-stimulated CD4þ T cells, KRGE significantly decreased total allogeneic T cell proliferation. Consistent with the effects of TCR stimulation, KRGE reduced the number of CD4þIL-17þ cells and increased the number of CD4þCD25þFoxp3þ cells under the Th17-polarizing condition. Conclusion: KRGE has immunological benefits through the reciprocal regulation of Th17 and Treg cells during CsA-induced immunosuppression.