NKp44 expression, phylogenesis and function in non-human primate NK cells
NKp44 expression, phylogenesis and function in non-human primate NK cells
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DOI：
10.1093/intimm/dxn144
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发表时间：
2009-03-01
影响因子：
4.4
通讯作者：
Biassoni, Roberto
中科院分区：
文献类型：
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作者：
De Maria, Andrea;Ugolotti, Elisabetta;Biassoni, Roberto
迄今为止，除智人以外的物种中天然细胞毒性受体 (NCR) NKp44 的分子和功能表征一直难以捉摸。在这里，我们提供了与人类关系最近的潘穴居人 NK 细胞上 NKp44 触发受体的完整表型、分子和功能表征，以及食蟹猴中 NKp44 基因组位点和转录的分析。与智人类似，黑猩猩 NK 细胞只有在激活后才能检测到 NKp44 表达。然而，与人类相比，黑猩猩的基础 NKp44 转录水平高出 5 倍，且细胞激活后的差异增加较低。激活后，与智人 NK 细胞相比，在穴居人中观察到 NKp44 基因表达总体降低 12 倍，且 NKp44 表面表达仅略有降低。 “体外”激活的纯化 NK 细胞的功能分析证实了 NKp44 与其他主要 NCR 相比的触发潜力。这些发现表明，在智人中存在着不同进化的转录后调控。对食蟹猴 NKp44 基因组序列和转录模式的分析显示转录水平非常低，出现框外转录本且没有表面表达。目前的比较分析表明，NKp44 基因组组织出现在猕猴物种形成过程中，其转录和转录后调节发生了相当大的进化。因此，NKp44可能代表最近在物种形成过程中才出现的NCR，仅在最接近智人的非人类灵长类动物中获得功能相关性。
Molecular and functional characterization of the natural cytotoxicity receptor (NCR) NKp44 in species other than Homo sapiens has been elusive, so far. Here, we provide complete phenotypic, molecular and functional characterization for NKp44 triggering receptor on Pan troglodytes NK cells, the closest human relative, and the analysis of NKp44-genomic locus and transcription in Macaca fascicularis. Similar to H. sapiens, NKp44 expression is detectable on chimpanzee NK cells only upon activation. However, basal NKp44 transcription is 5-fold higher in chimpanzees with lower differential increases upon cell activation compared with humans. Upon activation, an overall 12-fold lower NKp44 gene expression is observed in P. troglodytes compared with H. sapiens NK cells with only a slight reduction in NKp44 surface expression. Functional analysis of 'in vitro' activated purified NK cells confirms the NKp44 triggering potential compared with other major NCRs. These findings suggest the presence of a post-transcriptional regulation that evolved differently in H. sapiens. Analysis of cynomolgus NKp44-genomic sequence and transcription pattern showed very low levels of transcription with occurrence of out-of-frame transcripts and no surface expression. The present comparative analysis suggests that NKp44-genomic organization appears during macaque speciation, with considerable evolution of its transcriptional and post-transcriptional tuning. Thus, NKp44 may represent an NCR being only recently emerged during speciation, acquiring functional relevance only in non-human primates closest to H. sapiens.