NFKB1 regulates human NK cell maturation and effector functions
NFKB1 regulates human NK cell maturation and effector functions
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DOI：
10.1016/j.clim.2016.11.012
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发表时间：
2017-02-01
影响因子：
8.6
通讯作者：
Plebani, Alessandro
中科院分区：
文献类型：
--
作者：
Lougaris, Vassilios;Patrizi, Ornella;Plebani, Alessandro
NF κ B 1是经典NF-κ B通路的一个组成部分，最近报道在有限数量的CVID患者中发生突变。NFKB 2（非经典途径）中的CVID相关突变先前已显示会损害NK细胞的细胞毒性活性。尽管已经报道了NFKB 1在非人NK细胞中的生物学功能，但NFICB 1突变对人NK细胞生物学和疾病的作用尚未研究。因此，我们决定评估单等位基因NFKB 1突变在人类NK细胞成熟和功能中的作用。我们发现，NFKB 1突变的NK细胞在体外刺激时存在成熟受损、细胞毒性缺陷和IFN-γ产生减少。此外，人IL-2激活的NFKB 1突变的NI细胞不能上调激活标志物NKp 44的表达，并显示出降低的增殖能力。这些数据表明，NFKB 1在人NK细胞成熟和效应子功能中起着重要的新作用。(C)2016 Elsevier Inc. All rights reserved.
NFKB1, a component of the canonical NF-kappa B pathway, was recently reported to be mutated in a limited number of CVID patients. CVID-associated mutations in NFKB2 (non-canonical pathway) have previously been shown to impair NK cell cytotoxic activity. Although a biological function of NFKB1 in non-human NK cells has been reported, the role of NFICB1 mutations for human NK cell biology and disease has not been investigated yet. We decided therefore to evaluate the role of monoallelic NFKB1 mutations in human NK cell maturation and functions. We show that NFKB1 mutated NK cells present impaired maturation, defective cytotoxicity and reduced IFN-gamma production upon in vitro stimulation. Furthermore, human IL-2 activated NFKB1 mutated NI(cells fail to up regulate the expression of the activating marker NKp44 and show reduced proliferative capacity. These data suggest that NFKB1 plays an essential novel role for human NK cell maturation and effector functions. (C) 2016 Elsevier Inc. All rights reserved.