Aquaporin 9 Contributes to the Maturation Process and Inflammatory Cytokine Secretion of Murine Dendritic Cells
Aquaporin 9 Contributes to the Maturation Process and Inflammatory Cytokine Secretion of Murine Dendritic Cells
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DOI：
10.3389/fimmu.2018.02355
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发表时间：
2018-10-16
影响因子：
7.3
通讯作者：
Chieppa, Marcello
中科院分区：
文献类型：
--
作者：
De Santis, Stefania;Fiorentino, Maria R.;Chieppa, Marcello
树突状细胞（Dendritic cells，DC）是目前发现的最有效的抗原提呈细胞，能够触发针对特异性抗原的适应性免疫应答。当非自身抗原被捕获时，DC从“不成熟”状态转变为“成熟”状态以履行其功能。在参与DC成熟的几种表面蛋白中，水通道蛋白（AQP）的作用仍然知之甚少。本文研究了Aqps在小鼠骨髓来源的树突状细胞（BMDCs）中的表达谱。在分析的Aqp中，Aqp 9由DC表达最多。LPS暴露后6 h，其表达水平显著上调。Aqp 9的化学抑制导致炎性细胞因子分泌减少。来自AQP 9-KO小鼠的BMDC释放较少量的炎性细胞因子和趋化因子，并增加IL-10的释放。尽管炎性细胞因子的释放减少，但Aqp 9-KO小鼠未受到DSS诱导的结肠炎的保护。总之，我们的数据表明，AQP 9阻断可以是减少DC炎症反应的有效策略，但它不足以保护免受急性炎症损伤，如DSS诱导的结肠炎。
Dendritic cells (DCs) are the most potent antigen-presenting cells able to trigger the adaptive immune response to specific antigens. When non-self-antigens are captured, DCs switch from an "immature" to a "mature" state to fulfill their function. Among the several surface proteins involved in DCs maturation, the role of aquaporins (AQPs) is still poorly understood. Here we investigated the expression profile of Aqps in murine bone marrow derived dendritic cells (BMDCs). Among the Aqps analyzed, Aqp9 was the most expressed by DCs. Its expression level was significantly upregulated 6 h following LPS exposure. Chemical inhibition of Aqp9 led to a decreased inflammatory cytokines secretion. BMDCs from AQP9-KO mice release lower amount of inflammatory cytokines and chemokines and increased release of IL-10. Despite the reduced release of inflammatory cytokines, Aqp9-KO mice were not protected from DSS induced colitis. All together, our data indicate that AQP9 blockade can be an efficient strategy to reduce DCs inflammatory response but it is not sufficient to protect from acute inflammatory insults such as DSS induced colitis.