Impairment of NK cell function by NKG2D modulation in NOD mice
Impairment of NK cell function by NKG2D modulation in NOD mice
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DOI：
10.1016/s1074-7613(02)00505-8
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发表时间：
2003-01-01
期刊：
影响因子：
32.4
通讯作者：
Lanier, LL
中科院分区：
文献类型：
--
作者：
Ogasawara, K;Hamerman, JA;Lanier, LL
非肥胖糖尿病（NOD）小鼠是胰岛素依赖型糖尿病的模型，其自然杀伤（NK）细胞介导的功能存在缺陷。在这里，我们显示了NOD NK细胞中活化受体NKG 2D的损伤。虽然来自C57 BL/6和NOD小鼠的静息NK细胞表达相等水平的NKG 2D，但在活化后，NOD NK细胞而非C57 BL/6 NK细胞表达NKG 2D配体，这导致受体下调。由于受体调节，NKG 2D依赖性细胞毒性和细胞因子产生减少，导致功能障碍。NKG 2D的调节主要依赖于DAP 10的YxxM基序，DAP 10是激活磷酸肌醇3激酶的NKG 2B相关衔接子。这些结果表明，NK细胞可能通过暴露于NKG 2D配体而脱敏。
Nonobese diabetic (NOD) mice, a model of insulin-dependent diabetes mellitus, have a defect in natural killer (NK) cell-mediated functions. Here we show impairment in an activating receptor, NKG2D, in NOD NK cells. While resting NK cells from C57BL/6 and NOD mice expressed equivalent levels of NKG2D, upon activation NOD NK cells but not C57BL/6 NK cells expressed NKG2D ligands, which resulted in downmodulation of the receptor. NKG2D-dependent cytotoxicity and cytokine production were decreased because of receptor modulation, accounting for the dysfunction. Modulation of NKG2D was mostly dependent on the YxxM motif of DAP10, the NKG2B-associated adaptor that activates phosphoinositide 3 kinase. These results suggest that NK cells may be desensitized by exposure to NKG2D ligands.