Autotaxin-Lysophosphatidic Acid Axis Blockade Improves Inflammation by Regulating Th17 Cell Differentiation in DSS-Induced Chronic Colitis Mice
Autotaxin-Lysophosphatidic Acid Axis Blockade Improves Inflammation by Regulating Th17 Cell Differentiation in DSS-Induced Chronic Colitis Mice
复制标题
自分泌运动因子-溶血磷脂酸轴阻断通过调节 DSS 诱导的慢性结肠炎小鼠的 Th17 细胞分化改善炎症
DOI：
10.1007/s10753-019-01015-z
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发表时间：
2019-10-01
期刊：
影响因子：
5.1
通讯作者：
Deng, Shuang-Jiao
中科院分区：
文献类型：
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作者：
Dong, Ya-Lan;Duan, Xue-Yun;Deng, Shuang-Jiao
自分泌运动因子-溶血磷脂酸（ATX-LPA）轴与多种炎症相关疾病密切相关。在慢性溃疡性结肠炎（UC）患者的结肠粘膜中，发现ATX的表达和Th 17细胞的百分比增加。然而，ATX-LPA轴是否影响慢性UC中Th 17细胞的分化尚不清楚。为了研究ATX-LPA轴是否有助于Th 17细胞分化，通过间隔饮用含DSS的水建立慢性UC小鼠模型。使用ATX抑制剂作为干预。观察疾病活动指数（DAI）、结肠重长比、结肠长度、结肠组织病理学及MAdCAM-1的表达。采用不同方法检测结肠组织中ATX、LPA受体、CD 34、IL-17 A、IL-21、IL-6、ROR-γt、STAT 3的表达以及脾脏和肠系膜淋巴结（MLN）中Th 17细胞的百分比。ATX阻断能够减轻DSS诱导的慢性结肠炎的症状和炎症反应。DAI和结肠重长比明显降低，结肠长度增加。抑制剂组病理损害和结肠炎严重程度均轻于DSS组。抑制ATX可降低ATX、LPA受体和CD 34的表达，也可降低脾脏和MLN中Th 17细胞的百分比以及结肠组织中IL-17 A和IL-21的表达，以及Th 17细胞信号通路中的因子包括IL-6、ROR-γt和STAT 3。ATX-LPA轴阻断可通过抑制Th 17细胞分化减轻慢性UC的炎症反应。
AbstractAutotaxin-lysophosphatidic acid (ATX-LPA) axis is closely associated with several inflammation-related diseases. In the colonic mucosa of patients with chronic ulcerative colitis (UC), the expression of ATX and the percentage of Th17 cells are found to increase. However, it is unclear whether ATX-LPA axis affects the differentiation of Th17 cells in chronic UC. To investigate whether ATX-LPA axis contributes to Th17 cell differentiation, a mouse model of chronic UC was established by drinking water with DSS at intervals. ATX inhibitor was used as an intervention. The disease active index (DAI), colonic weight to length ratio, colon length, colon histopathology, and MAdCAM-1 were observed. Additionally, the expression of ATX, LPA receptor, CD34, IL-17A, IL-21, IL-6, ROR-γt, STAT3 in colonic tissue, and the percentage of Th17 cells in spleens and mesenteric lymph nodes (MLNs) were measured using different methods. ATX blockade was able to relieve symptoms and inflammatory response of DSS-induced chronic colitis. The DAI and colonic weight to length ratio were apparently decreased, while the colon length was increased. The pathological damage and colitis severity were lighter in the inhibitor group than that in the DSS group. Inhibiting ATX reduced the expression of ATX, LPA receptor, and CD34 and also decreased the percentages of Th17 cells in spleens and MLNs and the expressions of IL-17A and IL-21, as well as the factors in Th17 cell signaling pathway including IL-6, ROR-γt, and STAT3 in colonic tissue. ATX-LPA axis blockade could alleviate inflammation by suppressing Th17 cell differentiation in chronic UC.