Generation of induced pluripotent stem cell-derived mice by reprogramming of a mature NKT cell.
Generation of induced pluripotent stem cell-derived mice by reprogramming of a mature NKT cell.
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DOI：
10.1093/intimm/dxu057
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发表时间：
2014-10
影响因子：
4.4
通讯作者：
Taniguchi M
中科院分区：
文献类型：
--
作者：
Ren Y;Dashtsoodol N;Watarai H;Koseki H;Quan C;Taniguchi M
NKT细胞的特点是表达了由Vα14Jα18基因片段编码的NKT细胞特异性不变抗原受体α链。这些NKT细胞在先天和获得性免疫系统之间架起桥梁，介导有效和增强的免疫反应；然而，体内有限的NKT细胞数量阻碍了它们的分析。本研究通过对成熟的NKT细胞进行重编程，产生了两种诱导多能干细胞衍生小鼠（NKT- ipsc衍生小鼠），其中一种同时携带重排的Vα14Jα18和Vβ7基因，另一种在两个等位基因上携带重排的Vα14Jα18，但在种系Vβ位点上。对NKT- ipsc衍生小鼠的分析显示，功能亚群频率相对正常的NKT细胞数量显著增加，但在某些情况下显著增强，并且在外周淋巴器官获得功能性NKT细胞成熟。除γδT细胞缺失和常规CD4 αβT细胞发育紊乱外，nkt - ipsc衍生小鼠的其他免疫细胞发育正常。这些结果表明，与先前报道的转基因小鼠模型相比，NKT- ipsc衍生的小鼠是一个更好的NKT细胞发育和功能研究模型，并且在自然染色体环境中存在预先重排的Vα14Jα18有利于NKT细胞的发育命运。
The successful generation of iPSC-derived mouse strains to study NKT cells NKT cells are characterized by their expression of an NKT-cell-specific invariant antigen-receptor α chain encoded by Vα14Jα18 gene segments. These NKT cells bridge the innate and acquired immune systems to mediate effective and augmented responses; however, the limited number of NKT cells in vivo hampers their analysis. Here, two lines of induced pluripotent stem cell-derived mice (NKT-iPSC-derived mice) were generated by reprogramming of mature NKT cells, where one harbors both rearranged Vα14Jα18 and Vβ7 genes and the other carries rearranged Vα14Jα18 on both alleles but germline Vβ loci. The analysis of NKT-iPSC-derived mice showed a significant increase in NKT cell numbers with relatively normal frequencies of functional subsets, but significantly enhanced in some cases, and acquired functional NKT cell maturation in peripheral lymphoid organs. NKT-iPSC-derived mice also showed normal development of other immune cells except for the absence of γδT cells and disturbed development of conventional CD4 αβT cells. These results suggest that the NKT-iPSC-derived mice are a better model for NKT cell development and function study rather than transgenic mouse models reported previously and also that the presence of a pre-rearranged Vα14Jα18 in the natural chromosomal context favors the developmental fate of NKT cells.
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小鼠和人类缺乏适配器SAP的NKT细胞发育有缺陷，X连锁淋巴增生性综合征基因产物。
DOI：
10.1084/jem.20042432
发表时间：
2005-03-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Pasquier B;Yin L;Fondanèche MC;Relouzat F;Bloch-Queyrat C;Lambert N;Fischer A;de Saint-Basile G;Latour S
通讯作者：
Latour S
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
4.4
作者：
Lacorazza, HD;Tucek-Szabo, C;Nikolich-Zugich, J
通讯作者：
Nikolich-Zugich, J
影响因子：
32.4
作者：
LINETTE, GP;GRUSBY, MJ;KORSMEYER, SJ
通讯作者：
KORSMEYER, SJ