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Title: Transfer of IgG in the female genital tract by MHC class I-related neonatal Fc receptor (FcRn) confers protective immunity to vaginal infection

Author
item LI, ZILI - University Of Maryland
item PALANIYANDI, SENTHILKUMAR - University Of Maryland
item ZENG, RONGYU - University Of Maryland
item Tuo, Wenbin
item ROOPENIAN, DERRY - Collaborator
item ZHU, XIAOPING - University Of Maryland

Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/1/2011
Publication Date: 3/15/2011
Citation: Li, Z., Palaniyandi, S., Zeng, R., Tuo, W., Roopenian, D., Zhu, X. 2011. Transfer of IgG in the female genital tract by MHC class I-related neonatal Fc receptor (FcRn) confers protective immunity to vaginal infection. Proceedings of the National Academy of Sciences. 108(11):4388-4393.

Interpretive Summary: IgG is a predominant immunoglobulin in female genital tract. Despite the abundance of IgG, surprisingly little is know about whether and how IgG enters the lumen of the genital tract and the exact role of local IgG may play in preventing sexually transmitted diseases. The present study demonstrated that the neonatal Fcy receptor, FcRn, was expressed in the female genital tract epithelial cells and bound IgG in a pH-dependent manner. In vitro studies showed the FcRn mediated bidirectional IgG transport across the polarized human endometrial monolayers and endosomal acidification appeared to be a prerequisite for FcRn mediated IgG transcytosis. Furthermore, in vivo IgG transcytosis mediated by FcRn was confirmed by translocating exogenous IgG into the genital lumen in wild-type, but not in FcRn-knockout (KO) mice. The function of FcRn-transported IgG was demonstrated by passive immunization using herpes simples virus-2 (HSV-2) specific polyclonal sera, which provided higher protection against infection by HSV-2 186 strain in wild-type mice than that of FcRn KO mice. These studies defined a novel FcRn-mediated mechanism of IgG transport across femal genital epithelium and demonstrated a role of FcRn in IgG distribution and functioning during host defense against sexually transmitted diseases.

Technical Abstract: IgG is a major immunoglobulin subclass in mucosal secretions of human female genital tract, where it predominates over the IgA isotype. Despite the abundance of IgG, surprisingly little is known about whether and how IgG enters the lumen of the genital tract and the exact role of local IgG may play in preventing sexually transmitted diseases. The present study demonstrated that the neonatal Fc' receptor, FcRn, was expressed in the female genital tract epithelial cells of humans and mice and bound IgG in a pH-dependent manner. In vitro studies showed that FcRn mediated bidirectional IgG transport across the polarized human endometrial HEC-1-A monolayers and endosomal acidification appeared to be a prerequisite for FcRn mediated IgG transcytosis. Furthermore, in vivo IgG transcytosis mediated by FcRn was confirmed by translocating systemically administered exogenous IgG into the genital lumen in wild-type, but not in FcRn-knockout (KO) mice. The function of FcRn-transported IgG was demonstrated by passive immunization using herpes simplex virus-2 (HSV-2) specific polyclonal sera, which conferred significantly higher protection against intravaginal challenge infection by HSV-2 186 strain in wild-type mice than that of FcRn KO mice. These studies defined a novel FcRn-mediated bidirectional mechanism of IgG transport across female genital epithelial barriers and provided evidence for an indispensable role of FcRn in IgG distribution and functioning during host defense against sexually transmitted diseases.