mTOR-Myc axis drives acinar-to-dendritic cell transition and the CD4+ T cell immune response in acute pancreatitis
mTOR-Myc axis drives acinar-to-dendritic cell transition and the CD4+ T cell immune response in acute pancreatitis
复制标题
mTOR-Myc 轴驱动急性胰腺炎中腺泡到树突状细胞的转变和 CD4(+) T 细胞免疫反应
DOI：
10.1038/s41419-020-2517-x
复制
发表时间：
2020-06-02
影响因子：
9
通讯作者：
Fei, Jian
中科院分区：
文献类型：
--
作者：
Xu, Dan;Xie, Rongli;Fei, Jian
急性胰腺炎（AP）的炎症反应与腺泡细胞到树突状细胞的转变有关。CD4(+) t细胞介导的适应性免疫反应是胰腺炎症损伤所必需的。然而，腺泡-树突状细胞转化对CD4(+) t细胞应答的影响及其调控机制尚不明确。通过反复腹腔注射CAE建立小鼠AP动物模型。在AP诱导前给予mTOR抑制剂雷帕霉素。分离原代腺泡细胞并与分化的CD4(+) T细胞亚群共孵育。DC-SIGN在人类AP患者胰腺组织中的表达也被评估。我们发现腺泡细胞表达DC-SIGN并表现出树突状细胞（dc）的表型，促进胰腺组织中初始CD4(+) T细胞向CD4(+)/ ifn - γ (+) Th1和CD4(+)/IL-17A(+) Th17细胞分化，DC-SIGN是Myc的靶基因。mTOR抑制剂雷帕霉素通过Myc抑制ap诱导的DC-SIGN表达、CD4(+) Th1/Th17细胞分化和促炎反应。在人类AP患者胰腺组织中，腺泡细胞表达DC-SIGN。总之，腺泡细胞到树突状细胞的转化通过mTOR-Myc-DC-SIGN轴参与CD4(+) t细胞免疫应答，这可能是预防AP局部胰腺炎症的有效靶点。
The inflammatory response in acute pancreatitis (AP) is associated with acinar-to-dendritic cell transition. The CD4(+) T-cell-mediated adaptive immune response is necessary for pancreatic inflammatory damage. However, the effect of acinar-to-dendritic cell transition on the CD4(+) T-cell response and the regulatory mechanism remain undefined. A mouse animal model of AP was established by repeated intraperitoneal injection of CAE. The mTOR inhibitor rapamycin was administered before AP induction. Primary acinar cells were isolated and co-incubated with subsets of differentiated CD4(+) T cells. The expression of DC-SIGN was also assessed in pancreatic tissues from human AP patients. We found acinar cells expressed DC-SIGN and displayed the phenotype of dendritic cells (DCs), which promoted the differentiation of naive CD4(+) T cells into CD4(+)/IFN-gamma(+) Th1 and CD4(+)/IL-17A(+) Th17 cells in pancreatic tissues during AP. DC-SIGN was the target gene of Myc. The mTOR inhibitor rapamycin inhibited AP-induced DC-SIGN expression, CD4(+) Th1/Th17 cell differentiation and the pro-inflammatory response via Myc. Acinar cells expressed DC-SIGN in pancreatic tissues of human patients with AP. In conclusion, acinar-to-dendritic cell transition is implicated in the CD4(+) T-cell immune response via mTOR-Myc-DC-SIGN axis, which might be an effective target for the prevention of local pancreatic inflammation in AP.