Fate mapping analysis of lymphoid cells expressing the NKp46 cell surface receptor
Fate mapping analysis of lymphoid cells expressing the NKp46 cell surface receptor
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DOI：
10.1073/pnas.1112064108
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发表时间：
2011-11-08
影响因子：
11.1
通讯作者：
Vivier, Eric
中科院分区：
文献类型：
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作者：
Narni-Mancinelli, Emilie;Chaix, Julie;Vivier, Eric
NKp46 是一种细胞表面受体，表达于自然杀伤 (NK) 细胞、T 细胞的微小亚群以及产生 IL-22 并表达转录因子视黄酸相关孤儿受体 (ROR)-gamma t（称为 NK 细胞受体 (NKR)(+)ROR-gamma t(+) 细胞）的先天淋巴细胞群体上。在这里，我们描述了 Nkp46(iCre) 敲入小鼠，其中编码改进的 Cre (iCre) 重组酶的基因被插入到 Nkp46 基因座中。该小鼠用于在体内无创追踪表达 NKp46 的细胞。命运图谱实验证明了 NKp46 在 NK 细胞上的稳定表达，并允许重新评估 NK 细胞成熟的顺序步骤。 NKp46 基因追踪还表明肠道 NKR(+)ROR-gamma t(+) 和 NK 细胞代表两个不同的谱系。此外，肝脏 NK 细胞的遗传异质性也得到了证明。最后，Nkp46(iCre) 小鼠还代表了一种独特的条件诱变小鼠模型，特别是在 NKp46(+) 细胞中，为 NKp46(+) NK、T 和 NKR(+)ROR-gamma t(+) 细胞生物学的进一步发展铺平了道路。
NKp46 is a cell surface receptor expressed on natural killer (NK) cells, on a minute subset of T cells, and on a population of innate lymphoid cells that produce IL-22 and express the transcription factor retinoid-related orphan receptor (ROR)-gamma t, referred to as NK cell receptor (NKR)(+)ROR-gamma t(+) cells. Here we describe Nkp46(iCre) knock-in mice in which the gene encoding the improved Cre (iCre) recombinase was inserted into the Nkp46 locus. This mouse was used to noninvasively trace cells expressing NKp46 in vivo. Fate mapping experiments demonstrated the stable expression of NKp46 on NK cells and allowed a reappraisal of the sequential steps of NK cell maturation. NKp46 genetic tracing also showed that gut NKR(+)ROR-gamma t(+) and NK cells represent two distinct lineages. In addition, the genetic heterogeneity of liver NK cells was evidenced. Finally, Nkp46(iCre) mice also represent a unique mouse model of conditional mutagenesis specifically in NKp46(+) cells, paving the way for further developments in the biology of NKp46(+) NK, T, and NKR(+)ROR-gamma t(+) cells.