Shikonin Controls the Differentiation of CD4+CD25+ Regulatory T Cells by Inhibiting AKT/mTOR Pathway

Inflammation. 2019 Aug;42(4):1215-1227. doi: 10.1007/s10753-019-00982-7.

Abstract

CD4+CD25+ regulatory T (Treg) cells maintain the function of immune tolerance and the balance of immune cells. Defects in the number and function of Treg cells can induce the development and progression of inflammatory disease. Shikonin, the main active ingredient of Lithospermum, has anti-inflammatory and anti-tumor effects. Shikonin is also an effective drug for the treatment of psoriasis, which is a chronic inflammatory skin disease. However, the underlying mechanism is not yet clear. To evaluate the role of shikonin on the induction of Treg cells, we tested the number and function of Treg cells in vivo and in vitro. Shikonin can effectively promote the differentiation of iTreg cells by inhibiting the AKT/mTOR pathway in vitro. Moreover, in vivo, intragastrically administered shikonin effectively improved lesions in mice with imiquimod-induced psoriasis and increased the number of iTreg cells in the spleen and their secretion. Shikonin significantly increases the expression of Foxp3mRNA in skin of the psorisic mice. Therefore, we expect that shikonin can prevent the development of inflammation and treat psoriasis by regulating iTreg cells. Novel ideas for the treatment of psoriasis are also proposed.

Keywords: CD4+CD25+ regulatory T cells; psoriasis; shikonin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cell Count
  • Cell Differentiation / drug effects*
  • Forkhead Transcription Factors / genetics
  • Immune Tolerance
  • Mice
  • Naphthoquinones / pharmacology*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Psoriasis / chemically induced
  • Psoriasis / drug therapy
  • RNA, Messenger / analysis
  • Skin / drug effects
  • Skin / metabolism
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / drug effects*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Naphthoquinones
  • RNA, Messenger
  • shikonin
  • mTOR protein, mouse
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases