幽门螺杆菌诱生的胃源外泌体调控NLRP12影响Th17/Treg对小儿IBD的免疫保护作用及其机制

儿童IBD缺乏药物，疗效差，死亡率高。幽门螺杆菌对肠道炎症损伤具有缓解作用的临床现象已有发现，但机制尚不明确。我们前期发现，合并Hp感染的患儿IBD症状较轻;Hp能引发胃粘膜分泌富含lncRNA-MALAT1的外泌体，该外泌体能上调肠道中NLRP12的水平，并导致Th17/Treg比率的下调，减轻肠道炎症反应;分子实验初步发现NLRP12是miR-150的靶基因，MALAT1与miR-150序列互补，是其潜在的ceRNA。据此，本项目将从外泌体lncRNA在组织器官间传递信息的角度，1.明确Hp诱生的胃外泌体对IBD肠道炎症损伤的免疫保护作用；2.阐明外泌体中富集的MALAT1是胃—肠间信息传递的关键分子，揭示MALAT1/miR-150/NLRP12 信号轴调控儿童IBD肠道免疫平衡的分子机制。为儿童IBD的临床综合治疗提供新的策略与依据，也为Hp在胃外疾病中的作用模式提供研究方向。

Pediatric IBD is a disease with poor efficacy and high mortality due to the lack of effective drugs. Previous research showed that H. pylori can alleviate the symptoms of IBD in children, we also found lnc MALAT1-enriched exosomes from gastric epithelium induced by H. pylori could relieve the symptoms of IBD, causing the up-regulation of NLRP12 in the intestinal epithelial cell, leading to the down-regulation of Th17/Treg balance. The results of bioinformatics analysis showed that NLRP12 is a target gene of miR-150. LncRNA MALAT1 and miR-150 sequences are complementary, lncRNA MALAT1 is considered as a potential ceRNA. Accordingly, we hypothesized that lncRNA MALAT1/miR-150/NLRP12 signaling axis mediates the immunoprotection of H. pylori on IBD. This study will explore the following topics, including the immunoprotective effects of exosomes from gastric epithelial induced by H. pylori on IBD, the ceRNA molecular mechanism of lncRNA MALAT1/miR-150/NLRP12 signaling axis and the regulation of NLRP12 on Th17/Treg balance and its effect in IBD inflammatory injury .This research will reveal the.molecular mechanism of H. pylori lessening the symptoms of IBD in children and provide a new strategy and basis for the clinical comprehensive treatment of pediatric IBD.