SIGNR3-dependent immune regulation by Lactobacillus acidophilus surface layer protein A in colitis
SIGNR3-dependent immune regulation by Lactobacillus acidophilus surface layer protein A in colitis
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DOI：
10.15252/embj.201490296
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发表时间：
2015-04-01
期刊：
影响因子：
11.4
通讯作者：
Mohamadzadeh, Mansour
中科院分区：
文献类型：
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作者：
Lightfoot, Yaima L.;Selle, Kurt;Mohamadzadeh, Mansour
肠道免疫调节信号控制肠道稳态。这种调节机制的破坏可能导致炎症性肠病（IBD）。嗜酸乳杆菌含有独特的表面层蛋白（Slps），包括SlpA、SlpB、SlpX和脂磷壁酸（LTA），其与模式识别受体相互作用以动员免疫应答。在此，为了阐明SlpA在保护性免疫调节中的作用，产生了仅表达SlpA的NCK 2187菌株。NCK 2187及其纯化的SlpA与C型凝集素SIGNR 3结合，以施加调节信号，从而缓解结肠炎，维持健康的胃肠道微生物群，并保护肠道粘膜屏障功能。然而，在Signr 3（-/-）小鼠中未观察到这种保护，表明SlpA/SIGNR 3相互作用在结肠炎中起关键调节作用。我们的工作提出了对SlpA/SIGNR 3诱导的反应的重要见解，这些反应是自身炎性疾病（包括IBD）新型生物疗法潜在发展的组成部分。
Intestinal immune regulatory signals govern gut homeostasis. Breakdown of such regulatory mechanisms may result in inflammatory bowel disease (IBD). Lactobacillus acidophilus contains unique surface layer proteins (Slps), including SlpA, SlpB, SlpX, and lipoteichoic acid (LTA), which interact with pattern recognition receptors to mobilize immune responses. Here, to elucidate the role of SlpA in protective immune regulation, the NCK2187 strain, which solely expresses SlpA, was generated. NCK2187 and its purified SlpA bind to the C-type lectin SIGNR3 to exert regulatory signals that result in mitigation of colitis, maintenance of healthy gastrointestinal microbiota, and protected gut mucosal barrier function. However, such protection was not observed in Signr3(-/-) mice, suggesting that the SlpA/SIGNR3 interaction plays a key regulatory role in colitis. Our work presents critical insights into SlpA/SIGNR3-induced responses that are integral to the potential development of novel biological therapies for autoinflammatory diseases, including IBD.