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 μg) 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-α, IL-6, and IL-1β 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-γ. 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.