Repeated α-galactosylceramide administration results in expansion of NK T cells and alleviates inflammatory dermatisis in MRL-lpr/lpr mice
Repeated α-galactosylceramide administration results in expansion of NK T cells and alleviates inflammatory dermatisis in MRL-lpr/lpr mice
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DOI：
10.4049/jimmunol.171.8.4439
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发表时间：
2003-10-15
影响因子：
4.4
通讯作者：
Singh, RR
中科院分区：
文献类型：
--
作者：
Yang, JQ;Saxena, V;Singh, RR
表达不变的Valpha14-Jalpha18 TCRα链的NK T(NKT)细胞识别糖脂AGS，如NIHC I类分子CD1d提出的α-半乳糖基神经酰胺(α-GalCer)。在被α-GalCer激活后，不变的NKT细胞分泌多种细胞因子，并在某些免疫介导的疾病中提供保护。在这里，我们研究了NKT细胞在炎症性皮炎发展中的作用；在MRL-LPR/LPR小鼠中，它与狼疮有共同的特征；在人类中。结果表明，MRL-LPR/LPR小鼠的NKT(TCRbeta(+)CD1d/α-GalCer四聚体(+))细胞的数量和功能较MRL-fas/fas和/或非自身免疫性C3H/Hej和BALB/c小鼠减少，尤其是NK1.1(-)亚群。重复使用α-GalCer可导致NKT细胞的扩张，并减轻MRL-LPR/LPR小鼠的皮炎。我们的结果表明，NKT细胞缺陷可以通过重复α-GalCer治疗得到纠正，NKT细胞在狼疮易感小鼠的炎症性皮炎中可能起到保护作用。
NK T (NKT) cells expressing the invariant Valpha14-Jalpha18 TCR alpha-chain recognize glycolipid Ags such as a-galactosylceramide (alpha-GalCer) presented by the NIHC class I-like molecule CD1d. Upon activation by alpha-GalCer, invariant NKT cells secrete multiple cytokines and confer protection in certain immune-mediated disorders. Here we have investigated the role of NKT cells in the development of inflammatory dermatitis; in MRL-lpr/lpr mice, which shares features with lupus; in humans. Our results show that the numbers and functions of NKT (TCRbeta(+)CD1d/alpha-GalCer tetramer(+)) cells, particularly of the NK1.1(-) subset, are reduced in MRL-lpr/lpr mice compared with MRL-fas/fas and/or nonautoimmune C3H/Hej and BALB/c mice. Repeated treatments with alpha-GalCer result in the expansion of NKT cells and alleviate dermatitis in MRL-lpr/lpr mice. Our results indicate that NKT cell deficiency can be corrected by repeated alpha-GalCer treatment and that NKT cells may play a protective role in inflammatory dermatitis of lupus-prone mice.