IL-23与IL-12诱导NK细胞功能的异同及机制初探

The different roles of IL-23 and IL-12 in function induction of NK cells and the preliminary mechanisms study

目的探讨细胞因子IL-23与IL-12对NK细胞功能的影响及可能的机制。方法密度梯度离心法分离人外周血单个核细胞(PBMCs)或磁珠纯化NK细胞,不刺激或用IL-23或IL-12刺激,用流式细胞术和ELISA法检测NK细胞产生IFN-γ的情况;以K562或Jurkat细胞作为靶细胞,用流式细胞术检测NK细胞的杀伤功能并分析NK细胞在不同的刺激条件下杀伤相关分子的表达情况及pSTAT的表达情况。结果与未刺激组相比,IL-23和IL-12均可以诱导NK细胞呈剂量和时间依赖方式产生IFN-γ;但IL-12而非IL-23可以增强NK细胞对靶细胞K562或Jurkat细胞的杀伤功能。进一步研究表明,IL-12而非IL-23可以诱导杀伤相关分子TRAIL及CD107a/b的表达。此外,IL-12诱导NK细胞表达更高水平的pSTAT4,而IL-23诱导NK细胞表达更高水平的pSTAT3。结论与IL-12相比,IL-23亦可以诱导NK细胞产生细胞因子但不能增强NK细胞的杀伤功能,IL-23不能诱导杀伤相关分子TRAIL及CD107a/b的表达,IL-23可以诱导低水平的pSTAT4但高水平的pSTAT3的表达。

To compare the different roles of IL-23 and IL-12 in function induction of NK cells from human beings and to study the preliminary mechanisms, PBMCs were isolated from normal human peripheral blood and purified NK cells ware isolated from PBMCs by microbeads. The production of IFN-γ by NK cells was detected by flow cytometry(FCM) and ELISA under the different culture conditions. By taking K562 or Jurkat cells as target cells, the cytotoxicty ability of NK cells were analyzed by FCM. FCM also used to analyze the expression of cytotoxity related molecules TRAIL and CD107 a/b by NK cells under the different culture conditions. The expression of pSTATs by NK cells were detected by FCM as well. Data showed that both IL-23 and IL-12 could induce the production of IFN-γ by NK cells in a dose and time dependent manner. IL-12 but IL-23 could enhance the cytotoxic ability of NK cells against K562 and Jurkat cells. IL-12 but IL-23 could induce the expression of cytotoxic related molecules TRAIL and CD107 a/b. IL-12 could induce the high expression of pSTAT-4 while IL-23 could induce the high expression of pSTAT-3. In conclusion, compared with IL-12, IL-23 could increase the production of IFN-γ by NK cells but could not enhance the cytotoxic ability of NK cells. IL-23 could not induce the expression of TRAIL and CD107 a/b but could induce the expression of pSTAT-3. These results indicate that IL-23 and IL-12 might display different roles in function induction of NK cells by different molecular signaling pathway.