Tanshinone IIA alleviates vitiligo by suppressing AKT mediated CD8+ T cells activation in a mouse model

Tanshinone IIA has been reported to exhibit anti-inflammatory effects, while it is not clear whether Tanshinone IIA has protective role in vitiligo. Premelanosome (PMEL) CD8(+) T cells were adoptive transferred into Krt14- Kitl* mice with Kit ligand (KITL) over-expressed, to construct the vitiligo model. Pdk1(fl/fl) and Stat3(fl/fl) mice were crossed with Cd8(cre) mice to establish Pdk1(TKO) and Stat3(TKO) mice. Tanshinone IIA (200 mu g) was intravenous injected to treat vitiligo in mice every 3 days. The accumulation of macrophages and CD8(+) T cells in the ear skin was assayed by flow cytometry. Bone marrow-derived macrophages (BMDMs) were induced and stimulated with lipopolysaccharides (LPS) and IL-4. It was found that Tanshinone IIA alleviated the development of vitiligo, impaired PMEL CD8(+) T cells accumulation in the ear skin, and inhibited LPS-induced TNF-alpha, IL-6, and IL-1 beta expression and secretion in BMDMs, which could also inhibit IL-4-induced Arg-1 and Mrc-1 expression in BMDMs. In addition, Tanshinone IIA could inhibit the proliferation and cytotoxic function of CD8(+) T cells indicated by the expression of Perforin, Granzymeb, and IFN-gamma. Furthermore, Tanshinone IIA treated Pdk1(TKO) mice, not Stat3(TKO) mice, showed impaired PMEL CD8(+) T cells accumulation in the ear skin. In summary, Tanshinone IIA alleviates vitiligo development with impaired CD8(+) T cells accumulation and activation of Pdk1-Akt pathway.