MST1 modulates Th17 activation in psoriasis via regulating TLR4-NF-κB pathway

Hum Cell. 2021 Jan;34(1):28-36. doi: 10.1007/s13577-020-00423-w. Epub 2020 Sep 15.

Abstract

Psoriasis is a chronic inflammatory skin disease which mainly involves immune system. This research was to investigate the role of MST1 in the psoriasis, and the detailed mechanism whether related with Th17 and NF-κB. The skin samples and peripheral blood were obtained from psoriasis patients. Skin samples and T cells isolated from peripheral blood of patients were cultured in vitro. The results showed that the level of MST1 in the lesional skin of all three patients was higher than that of un-lesional skin, as well as the amount of CD4, CD8 and IL17 positive T cells. The amount of circulating Th17 was higher than that of control. The level of MST1, IL-17, IL-22 and TNFα was enhanced in activated T cells (p < 0.01), which indicated that MST1 increased markedly in activated T cells. The proliferation and migration of T cells were decreasing in MST1 knockdown cells, while increasing in overexpressed cells, as well as the production of IL-17, IL-22 and TNFα. MST1 enhanced the activation of TLR4-NF-κB signaling pathway, and TLR4 knockdown could reverse the effect of MST1 on NF-κB activation. This research indicated that MST1 could regulate the activation of Th17 in psoriasis partly through TLR4-NF-κB pathway. MST1 may be a target for treatment of psoriasis.

Keywords: MST1; Psoriasis; TLR4-NF-κb; Th17.

MeSH terms

  • Adult
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lymphocyte Activation / genetics*
  • Lymphocyte Activation / physiology
  • Male
  • Middle Aged
  • NF-kappa B / metabolism*
  • Protein Serine-Threonine Kinases / physiology*
  • Psoriasis / genetics*
  • Psoriasis / immunology*
  • Signal Transduction / genetics*
  • Signal Transduction / physiology*
  • Th17 Cells / immunology*
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • STK4 protein, human
  • Protein Serine-Threonine Kinases