NOD 小鼠中自然杀伤细胞功能成熟与细胞溶解功能的解耦
Uncoupling of Natural Killer cell functional maturation and cytolytic function in NOD mice.
发表日期：2023 Aug 03
作者：
Capucine Bourel, Victor Mullins-Dansereau, Maher Al Khaldi, Geneviève Chabot-Roy, Félix Lombard-Vadnais, Sylvie Lesage
来源：
Cellular & Molecular Immunology
摘要：
NK细胞是针对感染和肿瘤细胞的先天免疫细胞。成熟的NK（mNK）细胞经历四个不同的阶段的功能成熟，其中它们获得其细胞毒功能。非肥胖糖尿病（NOD）小鼠的mNK细胞表现出功能成熟的缺陷并且细胞毒功能受损。因此，我们测试了来自NOD小鼠的mNK细胞的细胞毒功能受损是否可以通过其功能成熟缺陷来解释。通过比较来自B6、B6g7和NOD小鼠的mNK细胞的功能，我们发现NOD小鼠的mNK细胞中炽锐粒体B的表达严重受损，与其无法控制体内肿瘤生长相一致。炽锐粒体B在NOD小鼠的mNK细胞中的低水平表达在所有功能成熟阶段中都存在，因此与其功能成熟缺陷无关。因此，该研究证明了mNK细胞的表型功能成熟可以脱离其获得细胞毒功能。 © 2023 The Authors. 《免疫学与细胞生物学》由约翰-威利澳大利亚有限公司代表澳大利亚和新西兰免疫学学会发表。
NK cells are innate immune cells that target infected and tumor cells. Mature NK (mNK) cells undergo functional maturation characterized by four distinct stages, during which they acquire their cytotoxic properties. mNK cells from non-obese diabetic (NOD) mice exhibit a defect in functional maturation and have impaired cytotoxic functions. Hence, we tested whether the impaired cytotoxic function observed in mNK cells from NOD mice can be explained by their defect in functional maturation. By comparing the function of mNK cells from B6, B6g7 and NOD mice, we show that the expression of granzyme B is severely impaired in mNK cells from NOD mice, agreeing with their inability to control tumor growth in vivo. The low level of granzyme B expression in mNK cells from NOD mice is found at all stages of functional maturation and is therefore independent of their functional maturation defect. Consequently, this study demonstrates that phenotypic functional maturation of mNK cells can be uncoupled from the acquisition of cytotoxic functions.© 2023 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.