Gaggero Silvia, Bruschi Maurizio, Petretto Andrea, Parodi Monica, Del Zotto Genny, Lavarello Chiara, Prato Carola, Santucci Laura, Barbuto Alessandra, Bottino Cristina, Candiano Giovanni, Moretta Alessandro, Vitale Massimo, Moretta Lorenzo, Cantoni Claudia
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
Dipartimento dei Laboratori di Ricerca, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Oncoimmunology. 2018 Jul 11;7(9):e1470730. doi: 10.1080/2162402X.2018.1470730. eCollection 2018.
The release of soluble ligands of activating Natural Killer (NK) cell receptors may represent a regulatory mechanism of NK cell function both in physiologic and in pathologic conditions. Here, we identified the extracellular matrix protein Nidogen-1 (NID1) as a ligand of NKp44, an important activating receptor expressed by activated NK cells. When released as soluble molecule, NID1 regulates NK cell function by modulating NKp44-induced IFN-γ production or cytotoxicity. In particular, it also modulates IFN-γ production induced by Platelet-Derived Growth Factor (PDGF)-DD following NKp44 engagement. We also show that NID1 may be present at the cell surface. In this form or when bound to a solid support (bNID1), NID1 fails to induce NK cell cytotoxicity or cytokine release. However, analysis by mass spectrometry revealed that exposure to bNID1 can induce in human NK cells relevant changes in the proteomic profiles suggesting an effect on different biological processes.
可溶性激活型自然杀伤（NK）细胞受体配体的释放可能代表了一种在生理和病理条件下调节NK细胞功能的机制。在此，我们鉴定出细胞外基质蛋白巢蛋白-1（NID1）是NKp44的配体，NKp44是活化NK细胞表达的一种重要激活受体。当作为可溶性分子释放时，NID1通过调节NKp44诱导的γ干扰素（IFN-γ）产生或细胞毒性来调节NK细胞功能。特别是，它还能调节NKp44激活后血小板衍生生长因子（PDGF）-DD诱导的IFN-γ产生。我们还表明，NID1可能存在于细胞表面。以这种形式或与固相支持物结合（bNID1）时，NID1无法诱导NK细胞的细胞毒性或细胞因子释放。然而，质谱分析显示，暴露于bNID1可诱导人类NK细胞蛋白质组图谱发生相关变化，提示其对不同生物学过程有影响。
