Laboratory of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742, USA.
Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4388-93. doi: 10.1073/pnas.1012861108. Epub 2011 Feb 28.
IgG is a major Ig subclass in mucosal secretions of the human female genital tract, where it predominates over the IgA isotype. Despite the abundance of IgG, surprisingly little is known about where and how IgG enters the lumen of the genital tract and the exact role local IgG plays in preventing sexually transmitted diseases. We demonstrate here that the neonatal Fc receptor, FcRn, is expressed in female genital tract epithelial cells of humans and mice and binds IgG in a pH-dependent manner. In vitro we show that FcRn mediates bidirectional IgG transport across polarized human endometrial HEC-1-A monolayers and primary human genital epithelial cells. Furthermore, endosomal acidification appears to be a prerequisite for FcRn-mediated IgG transcytosis; IgG transcytosis was demonstrated in vivo by translocation of systemically administered IgG into the genital lumen in WT but not FcRn-KO mice. The biological relevance of FcRn-transported IgG was demonstrated by passive immunization using herpes simplex virus-2 (HSV-2)-specific polyclonal serum, which conferred significantly higher protection against intravaginal challenge infection by the HSV-2 186 strain in WT mice than in FcRn-KO mice. These studies demonstrate that FcRn-mediated transport is a mechanism by which IgG can act locally in the female genital tract in immune surveillance and in host defense against sexually transmitted diseases.
IgG 是人类女性生殖道黏膜分泌物中的主要 Ig 亚类，在生殖道中 IgG 优于 IgA 同型。尽管 IgG 丰富，但人们对 IgG 如何进入生殖道腔以及局部 IgG 在预防性传播疾病中的确切作用知之甚少。我们在这里证明，新生 Fc 受体 FcRn 在人类和小鼠的生殖道上皮细胞中表达，并以 pH 依赖的方式结合 IgG。在体外，我们表明 FcRn 介导双向 IgG 跨极化人子宫内膜 HEC-1-A 单层和原代人生殖道上皮细胞的转运。此外，内体酸化似乎是 FcRn 介导的 IgG 转胞吞作用的前提条件；通过将系统给予的 IgG 转移到 WT 但不是 FcRn-KO 小鼠的生殖道腔中来体内证明 IgG 转胞吞作用。使用单纯疱疹病毒-2 (HSV-2)-特异性多克隆血清进行被动免疫证明了 FcRn 转运的 IgG 的生物学相关性，该血清在 WT 小鼠中对 HSV-2 186 株阴道内挑战感染的保护作用明显高于 FcRn-KO 小鼠。这些研究表明，FcRn 介导的转运是 IgG 可以在女性生殖道中发挥局部免疫监视和宿主防御作用的机制之一，以抵御性传播疾病。
