Hepatic Interleukin-7 Expression Regulates T Cell Responses
Hepatic Interleukin-7 Expression Regulates T Cell Responses
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DOI：
10.1016/j.immuni.2009.01.007
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发表时间：
2009-03-20
期刊：
影响因子：
32.4
通讯作者：
Murakami, Masaaki
中科院分区：
文献类型：
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作者：
Sawa, Yukihisa;Arima, Yasunobu;Murakami, Masaaki
响应于Toll样受体（TLR）信号传导的全身性细胞因子活性诱导感染后肝脏中各种蛋白质的表达。在这里，我们表明，白细胞介素-7（IL-7），其生产被认为是在体内发生在一个恒定的速度，是一个肝脏表达的蛋白质，直接控制T细胞的反应。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CD 4（+）T细胞和CD 8（+）T细胞存活，增强的CD 8（+）T细胞细胞细胞毒活性，以及实验性自身免疫性脑炎（一种Th 17细胞介导的自身免疫性疾病）的发展。因此，T细胞应答由肝细胞来源的IL-7调节，其在体内响应TLR信号传导而表达。我们认为，TLR诱导的IL-7在肝脏中的表达，这是一种急性期反应，可能是一个很好的诊断和治疗目标，有效的疫苗开发和条件的特点是TLR介导的T细胞失调，包括自身免疫性疾病。
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.