Della Chiesa Mariella, Carlomagno Simona, Frumento Guido, Balsamo Mirna, Cantoni Claudia, Conte Romana, Moretta Lorenzo, Moretta Alessandro, Vitale Massimo
DIMS (Dipartimento di Medicina Sperimentale), Università di Genova, Genova, Italy.
Blood. 2006 Dec 15;108(13):4118-25. doi: 10.1182/blood-2006-03-006700. Epub 2006 Aug 10.
Tryptophan (Trp) catabolism mediated by indoleamine 2,3-dioxygenase (IDO) plays a central role in the regulation of T-cell-mediated immune responses. In this study, we also demonstrate that natural killer (NK)-cell function can be influenced by IDO. Indeed, l-kynurenine, a Trp-derived catabolite resulting from IDO activity, was found to prevent the cytokine-mediated up-regulation of the expression and function of specific triggering receptors responsible for the induction of NK-cell-mediated killing. The effect of l-kynurenine appears to be restricted to NKp46 and NKG2D, while it does not affect other surface receptors such as NKp30 or CD16. As a consequence, l-kynurenine-treated NK cells display impaired ability to kill target cells recognized via NKp46 and NKG2D. Instead, they maintain the ability to kill targets, such as dendritic cells (DCs), that are mainly recognized via the NKp30 receptor. The effect of l-kynurenine, which is effective at both the transcriptional and the protein level, can be reverted, since NK cells were found to recover their functional competence after washing.
由吲哚胺2,3-双加氧酶（IDO）介导的色氨酸（Trp）分解代谢在调节T细胞介导的免疫反应中起核心作用。在本研究中，我们还证明自然杀伤（NK）细胞功能可受IDO影响。实际上，l-犬尿氨酸是IDO活性产生的一种Trp衍生代谢产物，它能阻止细胞因子介导的负责诱导NK细胞介导杀伤的特定触发受体的表达上调和功能增强。l-犬尿氨酸的作用似乎仅限于NKp46和NKG2D，而不影响其他表面受体，如NKp30或CD16。因此，经l-犬尿氨酸处理的NK细胞杀伤通过NKp46和NKG2D识别的靶细胞的能力受损。相反，它们保持了杀伤主要通过NKp30受体识别的靶细胞（如树突状细胞（DC））的能力。l-犬尿氨酸在转录和蛋白质水平均有作用，其作用可被逆转，因为发现NK细胞在洗涤后恢复了功能活性。
