Hepatic serum amyloid A1 upregulates interleukin-17 (IL-17) in γδ T cells through Toll-like receptor 2 and is associated with psoriatic symptoms in transgenic mice

Scand J Immunol. 2019 Jun;89(6):e12764. doi: 10.1111/sji.12764. Epub 2019 Apr 4.


Serum amyloid A (SAA) is an acute phase protein with pro-inflammatory cytokine-like properties. Recent studies have revealed that SAA promoted interleukin-17 (IL-17) production by various cells, including γδ T cells. γδ T cells are innate immune cells and express Toll-like receptor 2 (TLR2) on their surface, which is one of the SAA receptors. In this study, we investigated the relationship between γδ T cells and SAA1 through TLR2, by using hepatic SAA1-overexpressing transgenic (TG) mice. By injecting CU-CPT22, which is a TLR2 inhibitor, into the mice, we confirmed that SAA1 induced IL-17 in γδ T cells through TLR2. In vitro studies have confirmed that SAA1 increased IL-17 secretion in γδ T cells in combination with IL-23. We also observed a thickened epidermis layer and granulocyte penetration into the skin similar to the pathology of psoriasis in TG mice. In addition, strongly expressed SAA1 and penetration of γδ T cells in the skin of TG mice were detected. The exacerbation of psoriasis is associated with an increase in IL-17 levels. Therefore, these symptoms were induced by IL-17-producing γδ T cells increased by SAA1. Our study confirmed that SAA1 was a prominent protein that increased IL-17 levels through TLR2 in γδ T cells, confirming the possibility that SAA1 may exacerbate inflammatory diseases through γδ T cells.

Keywords: acute phase reactants; cytokines; experimental animals; inflammation; skin.

MeSH terms

  • Animals
  • Cells, Cultured
  • Interleukin-17 / biosynthesis*
  • Interleukin-23 Subunit p19 / biosynthesis
  • Interleukin-23 Subunit p19 / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Psoriasis / immunology
  • Psoriasis / pathology*
  • RNA, Messenger / biosynthesis
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Serum Amyloid A Protein / immunology*
  • Toll-Like Receptor 2 / antagonists & inhibitors
  • Toll-Like Receptor 2 / immunology*


  • Il17a protein, mouse
  • Il23a protein, mouse
  • Interleukin-17
  • Interleukin-23 Subunit p19
  • RNA, Messenger
  • Receptors, Antigen, T-Cell, gamma-delta
  • Serum Amyloid A Protein
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2