生命早期的微生物暴露对自然杀手T细胞功能有持续的影响
Torsten Olszak1, Dingding An, Sebastian Zeissig
1Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
概括
儿童早期接触微生物可以防止免疫疾病. 在没有细菌的小鼠中,缺乏微生物会导致免疫细胞的积累,并增加疾病的严重程度,这凸显了早期微生物接触的重要性.
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:
- 生命早期接触微生物与保护免疫媒介疾病,如炎症性肠病 (IBD) 和喘有关.
- 无细菌 (GF) 环境缺乏免疫系统通常遇到的微生物刺激.
研究的目的:
- 研究微生物暴露在调节粘膜组织中不变天然杀手T (iNKT) 细胞种群中的作用.
- 确定早期微生物殖民对IBD和过敏喘模型易感性的影响.
主要方法:
- 在IBD和过敏喘模型中,将GF小鼠与无特定病原体 (SPF) 小鼠进行比较.
- 分析iNKT细胞在结肠自身膜和肺中的积累.
- 在肠道和肺组织中测量化学因配体CXCL16的表达.
- 在不同年龄段 (新生儿与成年人) 用常规微生物群殖民GF小鼠.
主要成果:
- 与SPF小鼠相比,GF小鼠在结肠和肺部表现出iNKT细胞的积累增加.
- 这种iNKT细胞在GF小鼠中的积累与IBD和喘模型中的发病率增加相关.
- 在GF小鼠的粘膜中,CXCL16的表达升高,与iNKT细胞存在有关.
- 新生儿与微生物群的殖民,但不是成年人的殖民,阻止了iNKT细胞的积累和病理.
结论:
- 早期的微生物暴露对于建立粘膜iNKT细胞的耐受性至关重要.
- 敏感于年龄的微生物殖民计划免疫系统,以防止对环境因素的过度反应.
- 早期微生物接触的破坏可能导致免疫失调,并增加对免疫媒介疾病的易感性.
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