通过表皮CD1d和IL-10介导的保护性粘膜免疫
Torsten Olszak1, Joana F Neves1, C Marie Dowds2
11] Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [2].
Nature
|April 11, 2014
概括
皮质CD1d参与通过激活STAT3来保护肠道炎症,从而导致IL-10和HSP110的产生. 这一途径对于在炎症性肠病中维持粘膜平衡至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
背景情况:
- 粘膜平衡对于预防炎症性肠病 (IBD) 至关重要.
- 肠上皮细胞 (IECs) 在宿主-微生物群界面调节免疫反应.
- CD1d向NKT细胞呈现脂质抗原,涉及IBD病原发生.
研究的目的:
- 研究表皮CD1d在调节肠道炎症中的作用.
- 阐明表皮CD1d影响粘膜平衡的机制.
- 确定针对IBD中的表皮CD1d信号的治疗潜力.
主要方法:
- 在IEC和耐辐射中使用了具有特定基因缺失的小鼠模型.
- 分析了骨髓衍生的与上皮CD1d信号对NKT细胞介导性结肠炎的影响.
- 评估了STAT3,IL-10,HSP110和MTP在表皮细胞CD1d介导保护中的作用.
主要成果:
- 皮质CD1d的参与,与骨髓衍生的CD1d不同,具有对大肠炎的保护作用.
- 皮质CD1d激活STAT3会诱导IL-10,HSP110和CD1d的转录.
- 特定于IEC的IL-10,CD1d,MTP或HSP110的删除会加剧NKT细胞介导的大肠炎.
结论:
- 表皮CD1d信号传递代表了调节粘膜平衡的新途径.
- 在肠表皮中的IL-10在控制CD1d介导的炎症方面发挥着至关重要的作用.
- 这些发现对理解和治疗炎症性肠病有重大影响.
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