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IL-15 and CD155 expression regulate LAT expression in murine DNAM1+ NK cells, enhancing their effectors functions.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-02-20 , DOI: 10.1002/eji.201948233
Thuy T Luu 1 , Arnika K Wagner 1 , Laurent Schmied 1 , Stephan Meinke 1 , Jacquelyn E Freund 2 , Taku Kambayashi 2 , Inga Ravens 3 , Adnane Achour 4 , Gunter Bernhardt 3 , Benedict J Chambers 5 , Petter Höglund 1, 6 , Nadir Kadri 4
Affiliation  

NK cells are innate immune cells characterized by their ability to spontaneously lyse tumor and virally infected cells. We have recently demonstrated that IL-15-sufficient DC regulate NK cell effector functions in mice. Here, we established that among ITAM-proximal signaling molecules, the expression levels of the scaffold molecule Linker for Activation of T cells (LAT) and its transcription factor ELF-1 were reduced 4 days after in vivo depletion of DC. Addition of IL-15, a cytokine presented by DC to NK cells, regulates LAT expression in NK cells with a significant effect on the DNAM1+ subset compared to DNAM1- cells. We also found that LAT expression is regulated via interaction of the DNAM1 receptor with its ligand CD155 in both immature and mature NK cells, independently of NK cell education. Finally, we found that LAT expression within DNAM1+ NK cells might be responsible for enhanced calcium mobilization following the triggering of activating receptors on NK cells. Altogether, we found that LAT expression is tightly regulated in DNAM1+ NK cells, via interaction(s) with DC, which express CD155 and IL-15, resulting in rapid activation of the DNAM1+ subset during activating receptor triggering.

中文翻译:

IL-15和CD155的表达调节鼠DNAM1 + NK细胞中LAT的表达,增强其效应子功能。

NK细胞是先天性免疫细胞,其特征在于它们能够自发裂解肿瘤和病毒感染的细胞。我们最近证明,IL-15足够的DC调节小鼠中的NK细胞效应子功能。在这里,我们确定在ITAM-近端信号分子中,体内DC耗尽4天后,支架分子T细胞活化连接子(LAT)及其转录因子ELF-1的表达水平降低。与DCM1-细胞相比,IL-15是DC向NK细胞提供的一种细胞因子,它调节NK细胞中LAT的表达,并对DNAM1 +亚群产生显着影响。我们还发现,在未成熟和成熟的NK细胞中,通过DNAM1受体与其配体CD155的相互作用,可调节LAT的表达,而与NK细胞的培养无关。最后,我们发现DNAM1 + NK细胞内的LAT表达可能是由于NK细胞活化受体触发后钙动员增强所致。总的来说,我们发现通过与表达CD155和IL-15的DC的相互作用,DNAM1 + NK细胞中LAT的表达受到严格调节,从而在激活受体触发过程中导致DNAM1 +子集的快速激活。
更新日期:2020-02-20
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