Lopez-Lastra Silvia, Masse-Ranson Guillemette, Fiquet Oriane, Darche Sylvie, Serafini Nicolas, Li Yan, Dusséaux Mathilde, Strick-Marchand Helene, Di Santo James P
Innate Immunity Unit, Institut Pasteur, Paris, France.
INSERM U1223, Paris, France; and.
Blood Adv. 2017 Apr 6;1(10):601-614. doi: 10.1182/bloodadvances.2017004358. eCollection 2017 Apr 11.
Humanized mice harboring human hematopoietic systems offer a valuable small-animal model to assess human immune responses to infection, inflammation, and cancer. Human immune system (HIS) mice develop a broad repertoire of antigen receptor bearing B and T cells that can participate in adaptive immune responses after immunization. In contrast, analysis of innate immune components, including innate lymphoid cells (ILCs) and natural killer (NK) cells, is limited in current HIS mouse models, partly because of the poor development of these rare lymphoid subsets. Here we show that novel dendritic cell (DC)-boosted BALB/c (BRGSF) HIS mice harbor abundant NK cells and tissue-resident ILC subsets in lymphoid and nonlymphoid mucosal sites. We find that human NK cells and ILCs are phenotypically and functionally mature and provide evidence that human DC activation in BRGSF-based HIS mice can "cross talk" to human NK cells and ILCs. This novel HIS mouse model should provide the opportunity to study the immunobiology of human NK cell and ILC subsets in vivo in response to various environmental challenges.
携带人类造血系统的人源化小鼠为评估人类对感染、炎症和癌症的免疫反应提供了一种有价值的小动物模型。人类免疫系统（HIS）小鼠会发育出种类繁多的带有抗原受体的B细胞和T细胞，这些细胞在免疫后可参与适应性免疫反应。相比之下，在当前的HIS小鼠模型中，对包括先天淋巴细胞（ILC）和自然杀伤（NK）细胞在内的先天免疫成分的分析受到限制，部分原因是这些罕见淋巴细胞亚群的发育较差。在这里，我们展示了新型树突状细胞（DC）增强的BALB/c（BRGSF）HIS小鼠在淋巴和非淋巴黏膜部位含有丰富的NK细胞和组织驻留ILC亚群。我们发现人类NK细胞和ILC在表型和功能上是成熟的，并提供证据表明基于BRGSF的HIS小鼠中的人类DC激活可以与人类NK细胞和ILC“相互作用”。这种新型的HIS小鼠模型应该为研究人类NK细胞和ILC亚群在体内对各种环境挑战的免疫生物学提供机会。
