Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan.
Scand J Immunol. 2012 Jan;75(1):16-26. doi: 10.1111/j.1365-3083.2011.02607.x.
Invariant natural killer T (iNKT) cells are considered innate-like lymphocytes, and regulate the immunity against inflammation and tumorigenesis. However, the impact of iNKT cells in inflammation-associated tumorigenesis remains unclear. In this study, we examined the physiological role of iNKT cells in a mouse colitis-associated colorectal cancer model. C57BL/6 (B6) and Jα18 NKT cell-deficient KO (KO) mice were used. Colitis-associated colorectal cancer was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). The resulting inflammation and tumours were examined. The surface markers of mononuclear cells from the liver and the colon were assessed by FACS. The levels of IL-13 from the colon were measured by ELISA. α-galactosylceramide (GC), or its close analog OCH, was administered intraperitoneally on the first day of each cycle of DSS-administration. In the AOM/DSS model, hepatic iNKT cells were significantly decreased. In KO mice there were significantly greater numbers of colon tumours and more severe inflammation than in B6 mice. FACS analysis revealed that the population of NK1.1 (+) T cells (non-invariant NKT cells) in the colon was increased when compared to B6 mice. The secretion of IL-13 was increased in the colon of KO mice after AOM/DSS. The number of colon tumours was significantly decreased in the GC-treated group compared to the control group. GC-treatment significantly inhibited IL-13 secretion from the colonic mononuclear cells and the number of colonic NK1.1 (+) T cells was significantly decreased. These results suggest that iNKT cells may play a critical role in the prevention of tumour progression and inflammation in the AOM/DSS model.
固有自然杀伤 T(iNKT)细胞被认为是先天样淋巴细胞，可调节对炎症和肿瘤发生的免疫。然而，iNKT 细胞在炎症相关肿瘤发生中的作用尚不清楚。在这项研究中，我们检查了 iNKT 细胞在小鼠结肠炎相关结直肠癌模型中的生理作用。使用 C57BL/6（B6）和 Jα18 NKT 细胞缺陷型 KO（KO）小鼠。用氧化偶氮甲烷（AOM）和葡聚糖硫酸钠（DSS）诱导结肠炎相关结直肠癌。检查由此产生的炎症和肿瘤。通过 FACS 评估肝脏和结肠单核细胞的表面标志物。通过 ELISA 测量结肠中 IL-13 的水平。在 DSS 给药的每个周期的第一天，腹腔内给予 α-半乳糖神经酰胺（GC）或其密切类似物 OCH。在 AOM/DSS 模型中，肝 iNKT 细胞明显减少。与 B6 小鼠相比，KO 小鼠的结肠肿瘤数量明显更多，炎症更严重。FACS 分析显示，与 B6 小鼠相比，结肠中 NK1.1（+）T 细胞（非不变 NKT 细胞）的数量增加。AOM/DSS 后 KO 小鼠结肠中 IL-13 的分泌增加。与对照组相比，GC 治疗组的结肠肿瘤数量明显减少。GC 治疗可显著抑制结肠单核细胞中 IL-13 的分泌，并显著减少结肠 NK1.1（+）T 细胞的数量。这些结果表明，iNKT 细胞可能在 AOM/DSS 模型中预防肿瘤进展和炎症中发挥关键作用。
