Human neutrophils interact with both 6-sulfo LacNAc+ DC and NK cells to amplify NK-derived IFNγ: role of CD18, ICAM-1, and ICAM-3
Human neutrophils interact with both 6-sulfo LacNAc+ DC and NK cells to amplify NK-derived IFNγ: role of CD18, ICAM-1, and ICAM-3
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DOI：
10.1182/blood-2010-06-287243
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发表时间：
2011-02-03
期刊：
影响因子：
20.3
通讯作者：
Cassatella, Marco A.
中科院分区：
文献类型：
--
作者：
Costantini, Claudio;Calzetti, Federica;Cassatella, Marco A.
中性粒细胞作为调节先天性和适应性免疫应答的关键参与者的作用越来越被认识到。我们报道了人类中性粒细胞与自然杀伤（NK）细胞和6-磺基LacNAc（+）树突状细胞（slanDCs）建立网络，其最终用于上调NK衍生的干扰素γ（IFN γ）。该网络涉及直接的相互作用和由细胞衍生的细胞因子介导的正放大环。因此，我们表明，在脂多糖+白细胞介素-2（IL-2）或IL-15/IL-18刺激后，中性粒细胞直接与slanDCs和NK细胞相互作用并增强其活性。一方面，中性粒细胞通过CD 18/细胞间粘附分子-1（ICAM-1）相互作用增加slanDC释放IL-12 p70，所述相互作用刺激活化的NK细胞产生IFN γ。IFN γ进一步增强中性粒细胞和slanDC之间的相互作用以及slanDC衍生的IL-12 p70的释放，从而产生正反馈回路。另一方面，中性粒细胞通过CD 18/ICAM-3直接共刺激NK细胞，导致IFN γ的产生。嗜中性粒细胞、NK细胞和slanDC以及IL-12 p70和IFN γ在克罗恩病和银屑病的发炎组织中的共定位为先天免疫系统内的新型细胞和细胞因子合作提供了强有力的证据，其中嗜中性粒细胞充当NK细胞/slanDC介导的应答的放大器。（血。2011; 117（5）：1677-1686）
The role of neutrophils as key players in the regulation of innate and adaptive immune responses is increasingly being recognized. We report that human neutrophils establish a network with both natural killer (NK) cells and 6-sulfo LacNAc(+) dendritic cells (slanDCs), which ultimately serves to up-regulate NK-derived interferon gamma (IFN gamma). This network involves direct reciprocal interactions and positive amplification loops mediated by cell-derived cytokines. Accordingly, we show that after lipopolysaccharide + interleukin-2 (IL-2) or IL-15/IL-18 stimulation, neutrophils directly interact with and potentiate the activity of both slanDCs and NK cells. On the one hand, neutrophils augment the release of IL-12p70 by slanDCs via a CD18/ intercellular adhesion molecule-1 (ICAM-1) interaction that stimulates activated NK cells to produce IFN gamma. IFN gamma further potentiates the interaction between neutrophils and slanDCs and the release of slanDC-derived IL-12p70, thus creating a positive feedback loop. On the other hand, neutrophils directly costimulate NK cells via CD18/ICAM-3, leading to the production of IFN gamma. Colocalization of neutrophils, NK cells, and slanDCs, as well as of IL-12p70 and IFN gamma, in inflamed tissues of Crohn disease and psoriasis provides strong evidence for a novel cellular and cytokine cooperation within the innate immune system in which neutrophils act as amplifiers of NK cell/slanDC-mediated responses. (Blood. 2011; 117(5): 1677-1686)