Altered gene expression and function of peripheral blood natural killer cells in children with autism.
Altered gene expression and function of peripheral blood natural killer cells in children with autism.
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DOI：
10.1016/j.bbi.2008.08.001
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发表时间：
2009-01
影响因子：
15.1
通讯作者：
Ashwood, Paul
中科院分区：
文献类型：
--
作者：
Enstrom, Amanda M.;Lit, Lisa;Onore, Charity E.;Gregg, Jeff P.;Hansen, Robin L.;Pessah, Isaac N.;Hertz-Picciotto, Irva;Van de Water, Judy A.;Sharp, Frank R.;Ashwood, Paul
免疫相关异常在自闭症谱系障碍（ASD）中已被反复报道，包括免疫失调和自身免疫现象的证据。NK细胞可能在ASD等神经发育障碍中发挥重要作用。在这里，我们对52名ASD儿童和27名典型发育儿童的外周血进行了基因表达筛选和细胞功能分析，这些儿童参加了病例对照CHARGE研究。在ASD中，NK细胞受体和效应分子的RNA表达显著上调。流式细胞术分析显示，ASD患儿静息状态下NK细胞穿孔素、颗粒酶B和干扰素γ (IFNγ)的产生增加（p<0.01）。K562靶细胞刺激NK细胞后，与对照组相比，ASD中NK细胞的细胞毒性显著降低（p<0.02）。此外，在类似的刺激条件下，ASD儿童NK细胞中穿孔素、颗粒酶B和IFNγ的存在显著低于对照组（p<0.001）。这些发现提示自闭症儿童中可能存在NK细胞功能障碍。NK细胞异常可能是ASD的一个易感因素，并可能在发育的关键时期诱发自身免疫和/或不良神经免疫相互作用。
Immune related abnormalities have repeatedly been reported in autism spectrum disorders (ASD), including evidence of immune dysregulation and autoimmune phenomena. NK cells may play an important role in neurodevelopmental disorders such as ASD. Here we performed a gene expression screen and cellular functional analysis on peripheral blood obtained from 52 children with ASD and 27 typically developing control children enrolled in the case-control CHARGE study. RNA expression of NK cell receptors and effector molecules were significantly upregulated in ASD. Flow cytometric analysis of NK cells demonstrated increased production of perforin, granzyme B, and interferon gamma (IFNγ) under resting conditions in children with ASD (p<0.01). Following NK cell stimulation in the presence of K562 target cells, the cytotoxicity of NK cells was significantly reduced in ASD compared with controls (p<0.02). Furthermore, under similar stimulation conditions the presence of perforin, granzyme B, and IFNγ in NK cells from ASD children was significantly lower compared with controls (p<0.001). These findings suggest possible dysfunction of NK cells in children with ASD. Abnormalities in NK cells may represent a susceptibility factor in ASD and may predispose to the development of autoimmunity and/or adverse neuroimmune interactions during critical periods of development.
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影响因子：
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