Chromatin organization as an indicator of glucocorticoid induced natural killer cell dysfunction.
Chromatin organization as an indicator of glucocorticoid induced natural killer cell dysfunction.
复制标题
DOI：
10.1016/j.bbi.2017.09.004
复制
发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Mathews HL
中科院分区：
文献类型：
--
作者：
Misale MS;Witek Janusek L;Tell D;Mathews HL
众所周知，心理困扰会降低自然杀伤细胞的免疫功能，这种降低可能是由于压力导致糖皮质激素的释放。已知糖皮质激素可改变与免疫效应基因座相关的表观遗传标记，也可影响染色质组织。本研究的目的是评估糖皮质激素对自然杀伤细胞染色质组织的影响，并确定染色质组织与自然杀伤细胞效应器功能的关系，如干扰素-γ的产生。干扰素产生是由自然杀伤细胞产生的典型细胞因子，已知可以调节先天免疫和获得性免疫。糖皮质激素治疗人外周血单个核细胞导致干扰素伽马的产生显著减少。糖皮质激素治疗也导致了明显的自然杀伤细胞核表型。这种表型是组蛋白翻译后表观遗传标记H3K27me3定位于核周。H3K27me3的外周核定位与细胞内干扰素-γ水平直接相关。这种核表型是通过直接目测和使用自动化的高吞吐量技术Amny ImageStream确定的。这项技术结合了标准显微镜提供的每个细胞的信息量与标准流式细胞术常见的大样本所提供的统计学意义。最重要的是，这项技术提供了对单个细胞内信号强度定位的直接评估。结果表明，糖皮质激素至少部分通过改变H3K27me3的核组织来调节自然杀伤细胞的功能，并证明H3K27me3染色质组织是糖皮质激素诱导的自然杀伤细胞免疫失调的预测指标。
It is well-established that psychological distress reduces natural killer cell immune function and that this reduction can be due to the stress-induced release of glucocorticoids. Glucocorticoids are known to alter epigenetic marks associated with immune effector loci, and are also known to influence chromatin organization. The purpose of this investigation was to assess the effect of glucocorticoids on natural killer cell chromatin organization and to determine the relationship of chromatin organization to natural killer cell effector function, e.g. interferon gamma production. Interferon gamma production is the prototypic cytokine produced by natural killer cells and is known to modulate both innate and adaptive immunity. Glucocorticoid treatment of human peripheral blood mononuclear cells resulted in a significant reduction in interferon gamma production. Glucocorticoid treatment also resulted in a demonstrable natural killer cell nuclear phenotype. This phenotype was localization of the histone, post-translational epigenetic mark, H3K27me3, to the nuclear periphery. Peripheral nuclear localization of H3K27me3 was directly related to cellular levels of interferon gamma. This nuclear phenotype was determined by direct visual inspection and by use of an automated, high through-put technology, the Amnis ImageStream. This technology combines the per-cell information content provided by standard microscopy with the statistical significance afforded by large sample sizes common to standard flow cytometry. Most importantly, this technology provides for a direct assessment of the localization of signal intensity within individual cells. The results demonstrate glucocorticoids to dysregulate natural killer cell function at least in part through altered H3K27me3 nuclear organization and demonstrate H3K27me3 chromatin organization to be a predictive indicator of glucocorticoid induced immune dysregulation of natural killer cells.
登录
查看更多内容
DOI：
10.1016/0022-4731(89)90421-4
发表时间：
1989-12-01
影响因子：
4.1
作者：
DING, JY;YANG, SK;XU, RB
通讯作者：
XU, RB
DOI：
10.1083/jcb.123.6.1671
发表时间：
1993-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Belmont AS;Zhai Y;Thilenius A
通讯作者：
Thilenius A
影响因子：
15.1
作者：
Curtin, Niamh M.;Mills, Kingston H. G.;Connor, Thomas J.
通讯作者：
Connor, Thomas J.
影响因子：
3.3
作者：
Connor, TJ;Brewer, C;Harkin, A
通讯作者：
Harkin, A
影响因子：
3.3
作者：
De Bosscher, K;Vanden Berghe, W;Haegeman, G
通讯作者：
Haegeman, G