Hepatic Serum Amyloid A1 Upregulates Interleukin-17 (Il-17) In Gamma Delta T Cells Through Toll-Like Receptor 2 And Is Associated With Psoriatic Symptoms In Transgenic Mice

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 gamma delta T cells. gamma delta 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 gamma delta 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 gamma delta T cells through TLR2. In vitro studies have confirmed that SAA1 increased IL-17 secretion in gamma delta 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 gamma delta 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 gamma delta T cells increased by SAA1. Our study confirmed that SAA1 was a prominent protein that increased IL-17 levels through TLR2 in gamma delta T cells, confirming the possibility that SAA1 may exacerbate inflammatory diseases through gamma delta T cells.