Baker Kristi, Qiao Shuo-Wang, Kuo Timothy, Kobayashi Kanna, Yoshida Masaru, Lencer Wayne I, Blumberg Richard S
Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Semin Immunopathol. 2009 Jul;31(2):223-36. doi: 10.1007/s00281-009-0160-9. Epub 2009 Jun 3.
Careful regulation of the body's immunoglobulin-G (IgG) and albumin concentrations is necessitated by the importance of their respective functions. As such, the neonatal Fc receptor (FcRn) which, as a single receptor, is capable of regulating both of these molecules, has become an important focus of investigation. In addition to these essential protection functions, FcRn possesses a host of other functions that are equally as critical. During the very first stages of life, FcRn mediates the passive transfer of IgG from mother to offspring both before and after birth. In the adult, FcRn regulates the persistence of both IgG and albumin in the serum as well as the movement of IgG, and any bound cargo, between different compartments of the body. This shuttling allows for the movement not only of monomeric ligand but also of antigen/antibody complexes from one cell type to another in such a way as to facilitate the efficient initiation of immune responses towards opsonized pathogens. As such, FcRn continues to play the role of an immunological sensor throughout adult life, particularly in regions such as the gut which are exposed to a large number of infectious antigens. Increasing appreciation for the contributions of FcRn to both homeostatic and pathological states is generating an intense interest in the potential for therapeutic modulation of FcRn binding. A greater understanding of FcRn's pleiotropic roles is thus imperative for a variety of therapeutic purposes.
鉴于免疫球蛋白 G(IgG)和白蛋白各自功能的重要性,对它们在体内浓度进行精确调节是必要的。因此,作为单一受体的新生儿Fc受体(FcRn)能够调节这两种分子,已成为重要的研究焦点。除了这些基本的保护功能外,FcRn还具有许多同样关键的其他功能。在生命的最初阶段,FcRn介导出生前后IgG从母体到子代的被动转移。在成年人中,FcRn调节血清中IgG和白蛋白的持久性以及IgG及其结合的任何物质在体内不同区室之间的移动。这种穿梭作用不仅允许单体配体移动,还允许抗原/抗体复合物从一种细胞类型转移到另一种细胞类型,从而促进针对调理病原体的免疫反应有效启动。因此,FcRn在整个成年期持续发挥免疫传感器的作用,特别是在肠道等暴露于大量感染性抗原的区域。人们越来越认识到FcRn对稳态和病理状态的贡献,这激发了对FcRn结合进行治疗性调节潜力的浓厚兴趣。因此,为了各种治疗目的,深入了解FcRn的多效性作用势在必行。