肠上皮质PTPN2通过免疫导向的抗菌反应限制了病原体殖民
Pritha Chatterjee1, Marianne R Spalinger1,2, Charly Acevedo1
1Division of Biomedical Sciences, University of California, Riverside, Riverside, California.
肠表皮蛋白氨酸酸酶非受体2型 (PTPN2) 对于控制附着侵入性大肠杆菌 (AIEC) 殖民至关重要. 失去PTPN2会损害肠道免疫力,增加对病原生物的敏感性,并破坏肠道屏障.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 胃肠病学 胃肠病学
背景情况:
- 蛋白氨酸酸酶非受体2型 (PTPN2) 活性的丧失与肠道微生物组的改变和炎症性肠病 (IBD) 相相关.
- 附着侵入性大肠杆菌 (AIEC) 扩散是IBD病原发生的一个关键因素.
- 肠上皮细胞 (IEC) 控制病原生物的机制尚未完全理解.
研究的目的:
- 研究IEC特异性PTPN2在调节AIEC殖民中的作用.
- 阐明PTPN2缺乏对肠道屏障功能和对AIEC的免疫反应的影响.
主要方法:
- 产生的塔莫西芬诱导性,IEC特定的PTPN2淘汰赛小鼠 (Ptpn2^ΔIEC).
- 被非侵入性大肠杆菌K12感染的小鼠或被光标记的mAIEC (mAIEC^red).
- 量化了细菌负载,评估了基因/蛋白质表达 (AMP,细胞因子),测量了肠道透性,并分析了紧结蛋白.
主要成果:
- Ptpn2^ΔIEC小鼠在偏远结肠中显示出更多的mAIEC^red殖民.
- 在AIEC感染后的Ptpn2^ΔIEC小鼠中降低了α-defensin AMPs (Defa5,Defa6) 和MMP7表达.
- 在Ptpn2^ΔIEC小鼠中观察到肠道透率增加 (FD4) 和IL-22,IL-6,IL-17A细胞因子水平降低,IL-22部分恢复了屏障功能并减少了细菌负担.
结论:
- 特定于IEC的PTPN2对于维持粘膜免疫和肠道平衡至关重要.
- PTPN2通过协调的上皮-免疫反应促进抗菌防御,以限制病原生物殖民.
- 针对PTPN2介导的途径可能为IBD提供治疗策略.
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