Tanshinone IIA alleviates vitiligo by suppressing AKT mediated CD8 + T cells activation. - GreenMedInfo Summary
Tanshinone IIA alleviates vitiligo by suppressing AKT mediated CD8 T cells activation in a mouse model.
Dermatol Ther. 2021 Aug 4:e15086. Epub 2021 Aug 4. PMID: 34350676
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) CD8T cells were adoptive transferred into Krt14- Kitl* mice with Kit ligand (KITL) over-expressed, to construct the vitiligo model. Pdk1and Stat3mice were crossed with Cd8mice to establish Pdk1and Stat3mice. Tanshinone IIA (200 μg) was intravenous injected to treat vitiligo in mice every 3 days. The accumulation of macrophages and CD8T 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 CD8T 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 CD8T cells indicated by the expression of Perforin, Granzymeb, and IFN-γ. Furthermore, Tanshinone IIA treated Pdk1mice, not Stat3mice, showed impaired PMEL CD8T cells accumulation in the ear skin. In summary, Tanshinone IIA alleviates vitiligo development with impaired CD8T cells accumulation and activation of Pdk1-Akt pathway.