Table_1_Aquaporin-9 Contributes to the Maturation Process and Inflammatory Cytokine Secretion of Murine Dendritic Cells.DOC

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.

树突状细胞（DCs）是能够触发针对特定抗原的适应性免疫反应的最强大的抗原呈递细胞。当捕获非自身抗原时，DCs从“未成熟”状态转变为“成熟”状态以履行其功能。在参与DCs成熟过程的多种表面蛋白中，水通道蛋白（AQPs）的作用尚不明确。在本研究中，我们调查了小鼠骨髓来源的树突状细胞（BMDCs）中Aqps的表达谱。在所分析的AQPs中，Aqp9是DCs中表达量最高的。其表达水平在LPS暴露后6小时显著上调。Aqp9的化学抑制导致炎症细胞因子分泌减少。AQP9-KO小鼠的BMDCs释放的炎症细胞因子和趋化因子量降低，而IL-10的释放量增加。尽管炎症细胞因子的释放量减少，但AQP9-KO小鼠并未免受DSS诱导的结肠炎的侵害。综上所述，我们的数据表明，AQP9阻断可以是一种有效降低DCs炎症反应的策略，但它不足以保护免受急性炎症损伤，如DSS诱导的结肠炎。