Activation of natural killer T cells by α-galactosylceramide in the presence of CD1d provides protection against colitis in mice
Activation of natural killer T cells by α-galactosylceramide in the presence of CD1d provides protection against colitis in mice
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DOI：
10.1053/gast.2000.9114
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发表时间：
2000-07-01
期刊：
影响因子：
29.4
通讯作者：
Blumberg, RS
中科院分区：
文献类型：
--
作者：
Saubermann, LJ;Beck, P;Blumberg, RS
背景与目的：CD1d是一种主要的组织相容性复合体i类分子，可向自然杀伤（NK）1.1(+) T细胞亚群提供糖脂抗原。这些NK T细胞在几种自身免疫性疾病模型中表现出重要的免疫调节功能。方法：探讨CD1d和NK T细胞在肠道炎症中的作用是否相似，观察糖脂α -半乳糖神经酰胺（α - galcer）对葡聚糖硫酸钠（DSS）诱导的结肠炎的影响。检测野生型（WT）、CD1d（-/-）和RAG（-/-）小鼠对α - galcer或对照类似物α -甘露糖基神经酰胺（α - mancer）的反应。结果：与接受α - mancer的小鼠相比，接受α - galcer的WT小鼠，而不是CD1d（-/-）和RAG-/-小鼠，在体重、出血、腹泻和生存方面显著改善了dss诱导的结肠炎。通过抗体介导的消耗消除NK T细胞导致α - galcer作用的降低。此外，被α - galcer而非α - mancer预激活的NK T细胞过继性转移导致结肠炎减轻。使用荧光标记的α - galcer类似物，共聚焦显微镜将α - galcer定位到WT小鼠的结肠表面上皮，而不是CD1d（-/-）小鼠，这表明α - galcer与肠上皮中的CD1d结合，并可能在该部位具有功能活性。结论：这些结果表明NK T细胞被α - galcer以cd1限制的方式激活，在调节肠道炎症中具有重要的功能作用。
Background & Aims: CD1d is a major histocompatibility complex class I-like molecule that presents glycolipid antigens to a subset of natural killer (NK)1.1(+) T cells. These NK T cells exhibit important immunoregulatory functions in several autoimmune disease models. Methods: To investigate whether CD1d and NK T cells have a similar role in intestinal inflammation, the effects of the glycolipid, alpha-galactosylceramide (alpha-GalCer), on dextran sodium sulfate (DSS)-induced colitis were examined. Wild-type (WT), CD1d(-/-), and RAG(-/-) mice were examined for their response to either alpha-GalCer or the control analogue, alpha-mannosylceramide (alpha-ManCer). Results: WT mice, but not CD1d(-/-) and RAG-/- mice, receiving alpha-GalCer had a significant improvement in DSS-induced colitis based on body weight, bleeding, diarrhea, and survival when compared with those receiving alpha-ManCer. Elimination of NK T cells through antibody-mediated depletion resulted in a reduction of the effect of alpha-GalCer. Furthermore, adoptive transfer of NK T cells preactivated by alpha-GalCer, but not alpha-ManCer, resulted in diminished colitis. Using a fluorescent-labeled analogue of alpha-GalCer, confocal microscopy localized alpha-GalCer to the colonic surface epithelium of WT but not CD1d(-/-) mice, indicating alpha-GalCer binds CD1d in the intestinal epithelium and may be functionally active at this site. Conclusions: These results show an important functional role for NK T cells, activated by alpha-GalCer in a CD1d-restricted manner, in regulating intestinal inflammation.