Institute of Medical Virology, State Key Laboratory of Virology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
Department of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USA.
Cytokine. 2019 Nov;123:154776. doi: 10.1016/j.cyto.2019.154776. Epub 2019 Jul 22.
Interleukin (IL)-22, a member of the IL-10 family, plays a role in antiviral immune responses to a number of viral infections. However, it is unclear whether IL-22 is involved in the mucosal immunity against herpes simplex virus 2 (HSV-2) infection in the female reproductive tract (FRT). In this study, we studied whether IL-22 could inhibit HSV-2 infection of human cervical epithelial cells (End1/E6E7 cells). We showed that End1/E6E7 cells express the functional IL-22 receptor complex (IL-22R1 and IL-10R2). When treated with IL-22, End1/E6E7 cells expressed the higher levels of IFN-stimulated genes (ISGs: ISG15, ISG56, OAS-1, OAS-2, and Mx2) than untreated cells. In addition, IL-22-treated cells produced higher levels of the tight junction proteins (ZO-1 and Occludin) than untreated cells. Mechanistically, IL-22 could activate the JAK/STAT signaling pathway by inducing the phosphorylation of STAT1 and STAT3. These observations indicate the potential of IL-22 as an anti-HSV-2 agent in the FRT mucosal innate immunity against HSV-2 infection.
白细胞介素 (IL)-22 是 IL-10 家族的一员,在多种病毒感染的抗病毒免疫反应中发挥作用。然而,目前尚不清楚 IL-22 是否参与女性生殖道 (FRT) 对单纯疱疹病毒 2 (HSV-2) 感染的黏膜免疫。在这项研究中,我们研究了 IL-22 是否可以抑制 HSV-2 感染人宫颈上皮细胞 (End1/E6E7 细胞)。结果表明,End1/E6E7 细胞表达功能性的 IL-22 受体复合物 (IL-22R1 和 IL-10R2)。用 IL-22 处理后,与未经处理的细胞相比,End1/E6E7 细胞表达更高水平的干扰素刺激基因 (ISGs:ISG15、ISG56、OAS-1、OAS-2 和 Mx2)。此外,与未经处理的细胞相比,IL-22 处理的细胞产生更高水平的紧密连接蛋白 (ZO-1 和 Occludin)。从机制上讲,IL-22 通过诱导 STAT1 和 STAT3 的磷酸化来激活 JAK/STAT 信号通路。这些观察结果表明,IL-22 有可能成为 FRT 黏膜固有免疫中针对 HSV-2 感染的抗 HSV-2 药物。