Conditional deletion of the MHC class I-related receptor FcRn reveals the sites of IgG homeostasis in mice
Conditional deletion of the MHC class I-related receptor FcRn reveals the sites of IgG homeostasis in mice
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DOI：
10.1073/pnas.0810796106
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发表时间：
2009-02-24
影响因子：
11.1
通讯作者：
Ward, E. Sally
中科院分区：
文献类型：
--
作者：
Montoyo, Hector Perez;Vaccaro, Carlos;Ward, E. Sally
MHC-I类相关受体FcRN在体内调节免疫球蛋白的水平和持久性。这种受体挽救了细胞内溶酶体降解的免疫球蛋白，而免疫球蛋白与FcRN的结合特性与体内半衰期有关。在整个成年生活中，FcRN在多个不同部位表达。然而，FcRN维持免疫球蛋白稳态的细胞类型和部位还没有很好的定义。为了了解FcRN功能的位置，我们产生了一种小鼠品系，在这种品系中，Fc受体可以有条件地删除。结合Tie2启动子控制下表达Cre重组酶的小鼠(Tie2-Cre)，分析内皮细胞和造血细胞FcRN位点特异性缺失对免疫球蛋白G持久性的影响。FcRN纯合子在Tie2-Cre小鼠体内的药代动力学和稳态水平显示，FcRN在调节野生型免疫球蛋白半衰期方面的功能完全丧失。因此，维持小鼠内源性免疫球蛋白的主要部位是内皮细胞和造血细胞。
The MHC class I-related receptor FcRn regulates the levels and persistence of IgG in vivo. This receptor salvages IgG from lysosomal degradation within cells, and the binding properties of an IgG for FcRn correlate with in vivo half-life. FcRn is expressed at multiple different sites throughout adult life. However, the cell types and sites at which FcRn maintains IgG homeostasis are not well defined. Toward understanding the sites of FcRn function, we have generated a mouse strain in which this Fc receptor can be conditionally deleted. In combination with mice that express Cre recombinase under the control of the Tie2 promoter (Tie2-Cre), the effect of site-specific deletion of floxed FcRn in endothelial and hematopoietic cells on IgG persistence was analyzed. The pharmacokinetics and steady-state levels of IgG in Tie2-Cre mice that are homozygous for the floxed FcRn allele reveal a complete loss of FcRn function in regulating the half-lives of wild-type IgG. The primary sites for the maintenance of endogenous IgGs in mice are therefore endothelial and hematopoietic cells.