STAT6-dependent differentiation and production of IL-5 and IL-13 in murine NK2 cells
STAT6-dependent differentiation and production of IL-5 and IL-13 in murine NK2 cells
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DOI：
10.4049/jimmunol.173.8.4967
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发表时间：
2004-10-15
影响因子：
4.4
通讯作者：
Nakayama, T
中科院分区：
文献类型：
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作者：
Katsumoto, T;Kimura, M;Nakayama, T
NK细胞分化成分别产生IFN-γ或IL-5和IL-13的NK 1或NK 2细胞。然而，关于控制NK 1和NK 2细胞分化的分子机制知之甚少。为了解决这些问题，我们建立了体外小鼠NK 1/NK 2细胞分化培养体系。对于NK 1/NK 2细胞分化，需要用PMA和离子霉素进行初始刺激。体外分化的NK 2细胞产生IL-5和IL-13，但水平比Th 2或T细胞毒性（Tc）2细胞低20倍。未产生可检测的IL-4。新鲜制备的NK细胞表达IL-2 R β、IL-2 R γ C和IL-4 R α。经PMA和离子霉素刺激后，NK细胞表达IL-2 R α。NK 1细胞对Yac-1靶细胞具有较高的细胞毒活性。发育中的NK 2细胞中GATA 3蛋白的水平约为Th 2细胞中的六分之一。NK 1和NK 2细胞均表达大量的加塔阻遏物，其水平与CD 8的Tc 1和Tc 2细胞相当，明显高于Th 2细胞。NK 2细胞中IL-4和IL-13基因位点的组蛋白超乙酰化水平非常低，与初始CD 4 T细胞中的水平相当。发现NK 2细胞中IL-5和IL-13的产生具有状态依赖性。因此，类似于Th 2细胞，NK 2细胞的发育依赖于STATE，并且GATA 3的低水平表达和加塔的阻遏物的高水平表达可能影响NK 2细胞独特的2型细胞因子产生谱。
NK cells differentiate into either NK1 or NK2 cells that produce IFN-gamma or IL-5 and IL-13, respectively. Little is known, however, about the molecular mechanisms that control NK1 and NK2 cell differentiation. To address these questions, we established an in vitro mouse NK1/NK2 cell differentiation culture system. For NK1/NK2 cell differentiation, initial stimulation with PMA and ionomycin was required. The in vitro differentiated NK2 cells produced IL-5 and IL-13, but the levels were 20 times lower than those of Th2 or T cytotoxic (Tc)2 cells. No detectable IL-4 was produced. Freshly prepared NK cells express IL-2Rbeta, IL-2RgammaC, and IL-4Ralpha. After stimulation with PMA and ionomycin, NK cells expressed IL-2Ralpha. NK1 cells displayed higher cytotoxic activity against Yac-1 target cells. The levels of GATA3 protein in developing NK2 cells were approximately one-sixth of those in Th2 cells. Both NK1 and NK2 cells expressed large amounts of repressor of GATA, the levels of which were equivalent to CD8 Tc1 and Tc2 cells and significantly higher than those in Th2 cells. The levels of histone hyperacetylation of the IL-4 and IL-13 gene loci in NK2 cells were very low and equivalent to those in naive CD4 T cells. The production of IL-5 and IL-13 in NK2 cells was found to be STATE dependent. Thus, similar to Th2 cells, NK2 cell development is dependent on STATE, and the low level expression of GATA3 and the high level expression of repressor of GATA may influence the unique type 2 cytokine production profiles of NK2 cells.