TL1A primed dendritic cells activation exacerbated chronic murine colitis
TL1A primed dendritic cells activation exacerbated chronic murine colitis
复制标题
TL1A引发的树突状细胞激活加剧了慢性小鼠结肠炎
DOI：
10.1016/j.lfs.2020.118220
复制
发表时间：
2020-12-01
期刊：
影响因子：
6.1
通讯作者：
Zhang, Xiaolan
中科院分区：
文献类型：
--
作者：
Han, Fei;Song, Jia;Zhang, Xiaolan
目的：肿瘤坏死因子样配体1A（TL 1A）在炎症性肠病（IBD）中激活获得性免疫。然而，其在调节肠树突状细胞（DC）的作用尚未得到充分的表征。本研究旨在探讨TL 1A对小鼠结肠炎DC活化的调节作用。材料和方法：采用转TL 1A基因C57 BL/6小鼠和野生型小鼠，分别给予右旋糖酐硫酸钠（DSS），观察TL 1A对小鼠结肠炎DC活化的影响。分离骨髓来源的DC（BMDCs），检测其吞噬抗原和提呈抗原的能力。实时荧光定量PCR和Western blot检测NF-κ B（NF-κ B）通路和趋化因子受体（CCRs）的表达。来自TL 1A转基因小鼠的肠DC表达高水平的共刺激分子（CD 80和CD 86），具有增加的促炎细胞因子IL-1 β、TNF-α和IL 12/23 p40。TL 1A增强BMDCs的吞噬能力。TL 1A能增强BMDCs对抗原的加工和提呈能力。另外，TL 1A诱导NF-κ B（p65）和I κ B α的磷酸化。同时，在体内和体外均观察到CCR 2、CCR 5、CCR 7和CX 3CR 1的高表达。意义：TL 1A可能通过激活和迁移树突状细胞，从而增加促炎细胞因子的分泌，加重DSS诱导的慢性实验性结肠炎。
Aims: Tumor necrosis factor-like ligand 1A (TL1A) has been proved to activate adaptive immunity in inflammatory bowel disease (IBD). However, its role in the regulation of intestinal dendritic cells (DCs) has not been fully characterized. This study aims to investigate the modulation of TL1A in DCs activation in murine colitis.Materials and methods: Myeloid TL1A-Transgenic C57BL/6 mice and wild-type (WT) mice were administrated with dextran sulfate sodium (DSS) to explore the effects of TL1A in murine colitis. Bone marrow-derived DCs (BMDCs) were isolated to detect the ability of antigen phagocytosis and presentation. The expression of nuclear factor-kappa B (NF-kappa B) pathway and chemokines receptors (CCRs) was assessed by real-time PCR and Western blot.Key findings: Myeloid cells with constitutive TL1A expression developed worsened murine colitis with exacerbated TH1/TH17 cytokine responses. Intestinal DCs from TL1A transgenic mice expressed high levels of costimulatory molecules (CD80 and CD86) with increased pro-inflammatory cytokines of IL-1 beta, TNF-alpha and IL 12/23 p40. Mechanistic studies showed that TL1A enhanced the phagocytotic ability of BMDCs. Moreover, TL1A enhanced the capacity of antigen process and presentation in BMDCs. Besides, TL1A induced the phosphorylation of NF-kappa B(p65) and I kappa B alpha. Meanwhile, higher expression of CCR2, CCR5, CCR7, and CX3CR1 was observed both in vivo and in vitro.Significance: TL1A exacerbated DSS-induced chronic experimental colitis, probably through activation and migration of dendritic cells, and therefore increasing the secretion of pro-inflammatory cytokines.