Sawa Yukihisa, Arima Yasunobu, Ogura Hideki, Kitabayashi Chika, Jiang Jing-Jing, Fukushima Toru, Kamimura Daisuke, Hirano Toshio, Murakami Masaaki
Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Immunity. 2009 Mar 20;30(3):447-57. doi: 10.1016/j.immuni.2009.01.007. Epub 2009 Mar 12.
Systemic cytokine activity in response to Toll-like receptor (TLR) signaling induces the expression of various proteins in the liver after infections. Here we show that Interleukin-7 (IL-7), the production of which was thought to occur at a constant rate in vivo, was a hepatically expressed protein that directly controled T cell responses. Depletion of IL-7 expression in the liver abrogated several TLR-mediated T cell events, including enhanced CD4+ T cell and CD8+ T cell survival, augmented CD8+ T cell cytotoxic activity, and the development of experimental autoimmune encephalitis, a Th17 cell-mediated autoimmune disease. Thus, T cell responses are regulated by hepatocyte-derived IL-7, which is expressed in response to TLR signaling in vivo. We suggested that TLR-induced IL-7 expression in the liver, which is an acute-phase response, may be a good diagnostic and therapeutic target for efficient vaccine developments and for conditions characterized by TLR-mediated T cell dysregulation, including autoimmune diseases.
感染后，机体对Toll样受体（TLR）信号的全身性细胞因子活性会诱导肝脏中多种蛋白质的表达。在此我们表明，白细胞介素-7（IL-7），其在体内的产生曾被认为是以恒定速率进行的，是一种在肝脏中表达的蛋白质，可直接控制T细胞反应。肝脏中IL-7表达的缺失消除了几种TLR介导的T细胞事件，包括增强的CD4⁺ T细胞和CD8⁺ T细胞存活、增强的CD8⁺ T细胞细胞毒性活性，以及实验性自身免疫性脑脊髓炎（一种Th17细胞介导的自身免疫性疾病）的发展。因此，T细胞反应受肝细胞衍生的IL-7调节，IL-7是在体内对TLR信号作出反应而表达的。我们认为，肝脏中TLR诱导的IL-7表达作为一种急性期反应，可能是高效疫苗开发以及针对以TLR介导的T细胞失调为特征的病症（包括自身免疫性疾病）的良好诊断和治疗靶点。
