Immature murine NKT cells pass through a stage of developmentally programmed innate IL-4 secretion
Immature murine NKT cells pass through a stage of developmentally programmed innate IL-4 secretion
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未成熟的小鼠 NKT 细胞经历了发育程序化的先天性 IL-4 分泌阶段
DOI：
10.1189/jlb.0512242
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发表时间：
2012-11-01
影响因子：
5.5
通讯作者：
Hermans, Ian F.
中科院分区：
文献类型：
--
作者：
Dickgreber, Nina;Farrand, Kathryn J.;Hermans, Ian F.
我们评估了典型的Th 2细胞因子IL-4的NKT细胞的生产直接在体内使用IL-4替代菌株的报告小鼠，提供忠实和灵敏的读出细胞因子的生产没有在体外刺激的混杂效应。在幼稚动物中的分析揭示了IL-4分泌的“先天”阶段，其不需要通过施用已知的NKT细胞配体来触发。这种分泌是由未成熟的NKT细胞完成的，跨越胸腺中成熟过程的第1阶段（CD 4（+）CD 44（lo）NK1.1（-）细胞）和脾脏中成熟过程的第2阶段（CD 4（+）CD 44（hi）NK1.1（-）细胞）。与成熟细胞产生配体诱导的IL-4一样，这种先天活性不依赖于IL-4蛋白的初始来源，也不需要STAT 6信号。与C57 BL/6背景相比，在BALB/c背景的动物中观察到更持续的先天性IL-4产生水平，表明可能有助于BALB/c动物中“Th 2倾向”表型的遗传调节水平。这些观察结果表明成熟NKT细胞的IL-4表达的调节模式，这可能赋予这些细胞影响胸腺中周围细胞发育的能力。J.利瓦克92：999-1009; 2012.
We assessed the production of the canonical Th2 cytokine IL-4 by NKT cells directly in vivo using IL-4-substituting strains of reporter mice that provide faithful and sensitive readouts of cytokine production without the confounding effects of in vitro stimulation. Analysis in naive animals revealed an "innate" phase of IL-4 secretion that did not need to be triggered by administration of a known NKT cell ligand. This secretion was by immature NKT cells spanning Stage 1 of the maturation process in the thymus (CD4(+) CD44(lo) NK1.1(-) cells) and Stage 2 (CD4(+) CD44(hi) NK1.1(-) cells) in the spleen. Like ligand-induced IL-4 production by mature cells, this innate activity was independent of an initial source of IL-4 protein and did not require STAT6 signaling. A more sustained level of innate IL-4 production was observed in animals on a BALB/c background compared with a C57BL/6 background, suggesting a level of genetic regulation that may contribute to the "Th2-prone" phenotype in BALB/c animals. These observations indicate a regulated pattern of IL-4 expression by maturing NKT cells, which may endow these cells with a capacity to influence the development of surrounding cells in the thymus. J. Leukoc. Biol. 92: 999-1009; 2012.