Centenary Institute, The University of Sydney Faculty of Medicine and Health, Sydney, New South Wales, Australia.
Adult Cancer Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, 2052, Australia.
Sci Rep. 2019 May 13;9(1):7292. doi: 10.1038/s41598-019-43739-w.
The ubiquitous intracellular protease dipeptidyl peptidase 9 (DPP9) has roles in antigen presentation and B cell signaling. To investigate the importance of DPP9 in immune regeneration, primary and secondary chimeric mice were created in irradiated recipients using fetal liver cells and adult bone marrow cells, respectively, using wild-type (WT) and DPP9 gene-knockin (DPP9) enzyme-inactive mice. Immune cell reconstitution was assessed at 6 and 16 weeks post-transplant. Primary chimeric mice successfully regenerated neutrophils, natural killer, T and B cells, irrespective of donor cell genotype. There were no significant differences in total myeloid cell or neutrophil numbers between DPP9-WT and DPP9-reconstituted mice. In secondary chimeric mice, cells of DPP9-origin cells displayed enhanced engraftment compared to WT. However, we observed no differences in myeloid or lymphoid lineage reconstitution between WT and DPP9 donors, indicating that hematopoietic stem cell (HSC) engraftment and self-renewal is not diminished by the absence of DPP9 enzymatic activity. This is the first report on transplantation of bone marrow cells that lack DPP9 enzymatic activity.
普遍存在于细胞内的二肽基肽酶 9（DPP9）在抗原呈递和 B 细胞信号传导中发挥作用。为了研究 DPP9 在免疫重建中的重要性，利用野生型（WT）和 DPP9 基因敲入（DPP9）酶失活小鼠，分别通过辐照受体中的胎肝细胞和成年骨髓细胞，创建了原发性和继发性嵌合小鼠。在移植后 6 和 16 周评估免疫细胞重建情况。初级嵌合小鼠成功地再生了中性粒细胞、自然杀伤细胞、T 和 B 细胞，与供体细胞基因型无关。DPP9-WT 和 DPP9 重建小鼠之间的总髓样细胞或中性粒细胞数量没有显著差异。在次级嵌合小鼠中，与 WT 相比，DPP9 来源细胞的细胞显示出增强的植入。然而，我们在 WT 和 DPP9 供体之间没有观察到髓样或淋巴样谱系重建的差异，表明造血干细胞（HSC）植入和自我更新不会因缺乏 DPP9 酶活性而减弱。这是关于缺乏 DPP9 酶活性的骨髓细胞移植的首次报道。
