Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
PLoS One. 2012;7(9):e44113. doi: 10.1371/journal.pone.0044113. Epub 2012 Sep 6.
To investigate the role of inhibitory natural killer receptors (iNKRs) in inflammatory bowel disease (IBD), we analyzed the expression of NKG2A, one of the iNKRs, on T cells in a mouse colitis model and human IBD. During the active phase of dextran sulfate sodium (DSS)-induced mouse colitis, the frequency of NKG2A+ T cells was significantly decreased in the peripheral blood, and increased in the intestine, suggesting the mobilization of this T cell subset to the sites of inflammation. Administration of anti-NKG2A antibody increased the number of inflammatory foci in DSS-induced colitis, suggesting the involvement of NKG2A+ T cells in this colitis model. In ulcerative colitis (UC) patients, the frequency of peripheral blood NKG2A+ T cells was significantly decreased, compared with Crohn's disease (CD) patients and healthy controls, regardless of clinical conditions such as treatment modalities and disease activity. Notably, in sharp contrast to the DSS-induced mouse colitis model, the frequency of NKG2A+ cells among intestinal T cells was also decreased in UC patients. These results suggest that inadequate local infiltration of NKG2A+ T cells may be involved in the pathogenesis of UC.
为了探究抑制性自然杀伤细胞受体（iNKRs）在炎症性肠病（IBD）中的作用，我们分析了在小鼠结肠炎模型和人类 IBD 中 T 细胞上 NKG2A（iNKRs 之一）的表达。在葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的活动期，外周血中 NKG2A+T 细胞的频率显著降低，而在肠道中增加，提示该 T 细胞亚群向炎症部位的动员。给予抗 NKG2A 抗体可增加 DSS 诱导的结肠炎中的炎症灶数量，提示 NKG2A+T 细胞参与了该结肠炎模型。在溃疡性结肠炎（UC）患者中，与克罗恩病（CD）患者和健康对照者相比，外周血 NKG2A+T 细胞的频率显著降低，而与治疗方式和疾病活动等临床状况无关。值得注意的是，与 DSS 诱导的小鼠结肠炎模型形成鲜明对比的是，UC 患者的肠道 T 细胞中 NKG2A+细胞的频率也降低了。这些结果表明，NKG2A+T 细胞在局部浸润不足可能与 UC 的发病机制有关。
