Anti-inflammatory Role of IL-15Rα Up-regulated by Poly I:C in Herpes Simplex Virus-induced Behcet's Disease-like Mouse Model

Abstract

Behcet’s disease (BD) is a chronic, multi-systemic disorder that has arthritic, intestinal, mucocutaneous, ocular, vascular, and central nervous system affects. Interleukin-15 receptor alpha (IL-15Rα) forms stable complex with IL-15 on the cell surface of activated monocytes and mediates the proliferation of memory CD8+ T cells. Recent studies informed that Polyinosinic:polycytidylic acid (Poly I:C) is an immunostimulant which boosts the generation of memory T cells though induction of IL-15 and IL-15Rα. We found that the frequencies of IL-15Rα were significantly lower in HSV-induced BD mouse model than control mice. Therefore, this study was conducted to determine whether Poly I:C supplementation could induce memory cells through up-regulation of IL-15Rα, and reduce inflammation in HSV-induced BD symptoms. To evaluate whether the expression of IL-15Rα could be increased by poly I:C in vivo, Poly I:C was administered into normal and BD mice. Then, Poly I:C administered BD mice were subsequently observed the change of symptoms until 17 days after the last injection. The frequencies of IL-15Rα and memory CD8+ T cells were significantly up-regulated in Poly I:C injected mice. Poly I:C improved the symptoms and decreased severity score through down-regulation of pro-inflammatory cytokines and elevated regulatory and memory T cells. In conclusion, these results suggest that IL-15Rα is an important factor for the regulation of symptoms in HSV-induced BD mice.