NK cell maturation and function in C57BL/6 mice are altered by caloric restriction.
NK cell maturation and function in C57BL/6 mice are altered by caloric restriction.
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DOI：
10.4049/jimmunol.1201837
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发表时间：
2013-01-15
期刊：
影响因子：
--
通讯作者：
Gardner EM
中科院分区：
文献类型：
--
作者：
Clinthorne JF;Beli E;Duriancik DM;Gardner EM
NK细胞是先天淋巴细胞的异质群体，具有对于早期保护免受病毒感染至关重要的多种功能属性。我们以前曾报道过6个月大的C57 BL/6热量限制（CR）小鼠流感诱导的NK细胞细胞毒性降低。在目前的研究中，我们扩展了我们的研究结果CR对NK细胞表型和功能的影响，在没有感染。我们证明，减少成熟的NK细胞亚群导致CR小鼠中CD 127 + NK细胞的频率增加，从而使总NK细胞库的功能发生偏移。CR小鼠的NK细胞产生较高水平的TNF-α和GM-CSF，而IL-2 + IL-12或抗NK 1.1刺激后IFN-γ的产生受到损害。来自CR小鼠的NK细胞对YAC-1细胞刺激具有高度应答性，因此来自CR小鼠的CD 27 − CD 11 B + NK细胞产生颗粒酶B并以高于来自自由采食小鼠的CD 27 − CD 11 B + NK细胞的频率脱颗粒。CR已被证明是一种有效的饮食干预，但CR延长寿命的机制尚未完全了解。据我们所知，这些研究结果是第一次深入分析热量摄入对NK细胞表型和功能的影响，并提供了关于CR在感染或癌症之前改变NK细胞功能的潜在方式的重要意义。
NK cells are a heterogenous population of innate lymphocytes with diverse functional attributes critical for early protection from viral infections. We have previously reported a decrease in influenza-induced NK cell cytotoxicity in 6-mo-old C57BL/6 calorically restricted (CR) mice. In the current study, we extend our findings on the influence of CR on NK cell phenotype and function in the absence of infection. We demonstrate that reduced mature NK cell subsets result in increased frequencies of CD127+ NK cells in CR mice, skewing the function of the total NK cell pool. NK cells from CR mice produced TNF-α and GM-CSF at a higher level, whereas IFN-γ production was impaired following IL-2 plus IL-12 or anti-NK1.1 stimulation. NK cells from CR mice were highly responsive to stimulation with YAC-1 cells such that CD27−CD11b+ NK cells from CR mice produced granzyme B and degranulated at a higher frequency than CD27−CD11b+ NK cells from ad libitum fed mice. CR has been shown to be a potent dietary intervention, yet the mechanisms by which the CR increases life span have yet to be fully understood. To our knowledge, these findings are the first in-depth analysis of the effects of caloric intake on NK cell phenotype and function and provide important implications regarding potential ways in which CR alters NK cell function prior to infection or cancer.
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