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肠上皮质PTPN2通过免疫导向的抗微生物反应限制了病原生物的殖民化.

Pritha Chatterjee1, Marianne R Spalinger1,2, Charly Acevedo1

  • 1Division of Biomedical Sciences, University of California, Riverside, Riverside, CA, USA.

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概括

在肠道上皮细胞中失去蛋白氨酸酸酶非受体2型 (PTPN2) 会增加对致病性大肠杆菌的易感性. PTPN2对肠道免疫至关重要,调节抗微生物和屏障功能,以控制细菌殖民.

关键词:
粘附性侵入性大肠杆菌 (AIEC) 是一种抗微生物是一种抗菌.屏障功能 屏障功能介质蛋白-22 介质蛋白-22 的作用肠道的透性 肠道的透性这是一种病原生物.狭窄的十字路口 狭窄的十字路口

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科学领域:

  • 胃肠病学 胃肠病学
  • 免疫学 免疫学 免疫学
  • 微生物学 微生物学

背景情况:

  • 蛋白氨酸酸酶非受体2型 (PTPN2) 活性的丧失与炎症性肠病 (IBD) 和改变的肠道微生物群有关.
  • 附着侵入性大肠杆菌 (AIEC) 扩散与IBD病原发生有关,但宿主限制的机制尚不清楚.

研究的目的:

  • 研究肠上皮细胞 (IEC) 特定PTPN2在调节AIEC殖民和宿主防御中的作用.
  • 了解PTPN2如何影响肠道屏障和对细菌病原生物的免疫反应.

主要方法:

  • 使用泰莫西芬诱导性IEC特异性Ptpn2淘汰赛小鼠 (Ptpn2∆IEC) 和对照 littermates.
  • 被非侵入性大肠杆菌K12或光标记的mAIEC (mAIECred) 感染的小鼠和量化细菌负载.
  • 评估mRNA/蛋白质表达,细胞因子水平 (IL-22,IL-6,IL-17A) 和肠道屏障功能,使用光德克斯探针.

主要成果:

  • Ptpn2∆IEC小鼠与对照小鼠相比,在偏远结肠中显示出更多的mAIECred殖民.
  • 在Ptpn2∆IEC小鼠中观察到α-defensin抗微生物 (AMPs) 和MMP7的减少表达后mAIECred感染.
  • 在mAIECred感染后的Ptpn2∆IEC小鼠中,增加了肠道透性 (FD4) 和降低了IL-22,IL-6和IL-17A细胞因子水平.
  • 再组合IL-22的使用逆转了透性缺陷,并减少了细菌负担.

结论:

  • 肠上皮质PTPN2对于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,限制病原生物殖民.
  • 针对PTPN2介导的途径可能为IBD和相关疾病提供治疗策略.