PMID- 34350676 OWN - NLM STAT- MEDLINE DCOM- 20211101 LR - 20211101 IS - 1529-8019 (Electronic) IS - 1396-0296 (Linking) VI - 34 IP - 5 DP - 2021 Sep TI - Tanshinone IIA alleviates vitiligo by suppressing AKT mediated CD8(+) T cells activation in a mouse model. PG - e15086 LID - 10.1111/dth.15086 [doi] AB - 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 mug) 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-1beta 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. CI - (c) 2021 Wiley Periodicals LLC. FAU - Zhang, Diancai AU - Zhang D AD - Yidu Central Hospital of Weifang, Qingzhou, China. FAU - Wang, Yujie AU - Wang Y AD - Yidu Central Hospital of Weifang, Qingzhou, China. FAU - Li, Guangzhi AU - Li G AD - Yidu Central Hospital of Weifang, Qingzhou, China. FAU - Zhang, Baoxiang AU - Zhang B AUID- ORCID: 0000-0002-5453-5399 AD - Yidu Central Hospital of Weifang, Qingzhou, China. LA - eng PT - Journal Article DEP - 20210812 PL - United States TA - Dermatol Ther JT - Dermatologic therapy JID - 9700070 RN - 0 (Abietanes) RN - 03UUH3J385 (tanshinone) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Abietanes/pharmacology MH - Animals MH - CD8-Positive T-Lymphocytes MH - Mice MH - Proto-Oncogene Proteins c-akt MH - *Vitiligo/drug therapy OTO - NOTNLM OT - Akt OT - BMDMs OT - Pdk1 OT - Tanshinone IIA OT - vitiligo EDAT- 2021/08/06 06:00 MHDA- 2021/11/03 06:00 CRDT- 2021/08/05 06:49 PHST- 2020/12/07 00:00 [received] PHST- 2021/08/02 00:00 [accepted] PHST- 2021/08/06 06:00 [pubmed] PHST- 2021/11/03 06:00 [medline] PHST- 2021/08/05 06:49 [entrez] AID - 10.1111/dth.15086 [doi] PST - ppublish SO - Dermatol Ther. 2021 Sep;34(5):e15086. doi: 10.1111/dth.15086. Epub 2021 Aug 12.