Department of Immunology, Oslo University Hospital Rikshospitalet, University of Oslo, Oslo, Norway.
Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Scand J Immunol. 2021 Feb;93(2):e13017. doi: 10.1111/sji.13017. Epub 2021 Jan 17.
The neonatal Fc receptor (FcRn) was first recognized for its role in transfer of maternal IgG to the foetus or newborn, providing passive immunity early in life. However, it has become clear that the receptor is versatile, widely expressed and plays an indispensable role in both immunological and non-immunological processes throughout life. The receptor rescues immunoglobulin G (IgG) and albumin from intracellular degradation and shuttles the ligands across polarized cell barriers, in all cases via a pH-dependent binding-and-release mechanism. These processes secure distribution and high levels of both IgG and albumin throughout the body. At mucosal sites, FcRn transports IgG across polarized epithelial cells where it retrieves IgG in complex with luminal antigens that is delivered to tissue-localized immune cells. In dendritic cells (DCs), FcRn orchestrates processing of IgG-opsonized immune complexes (ICs) in concert with classical Fcγ receptors, which results in antigen presentation and cross-presentation of antigenic peptides on MHC class II and I to CD4+ and CD8+ T cells, respectively. Hence, FcRn regulates transport of the ligands within and across different types of cells, but also processing of IgG-ICs by immune cells. As such, the receptor is involved in immune surveillance and protection against infections. In this brief review, we highlight how FcRn expressed by hematopoietic and non-hematopoietic cells contributes to immune regulation at mucosal barriers-biology that can be utilized in development of biologics and subunit vaccines for non-invasive delivery.
新生儿 Fc 受体（FcRn）最初因其在将母体 IgG 转移到胎儿或新生儿中的作用而被认识，为生命早期提供被动免疫。然而，现在已经清楚的是，该受体具有多功能性，广泛表达，并在免疫和非免疫过程中发挥不可或缺的作用。该受体可从细胞内降解中挽救免疫球蛋白 G（IgG）和白蛋白，并通过依赖 pH 的结合-释放机制将配体转运穿过极化细胞屏障，在所有情况下均如此。这些过程确保了 IgG 和白蛋白在全身的分布和高水平。在黏膜部位，FcRn 将 IgG 转运穿过极化上皮细胞，在那里它与腔抗原结合的 IgG 一起回收，这些抗原被递送到组织定位的免疫细胞。在树突状细胞（DCs）中，FcRn 与经典 Fcγ 受体协同协调 IgG 调理免疫复合物（ICs）的处理，导致抗原呈递和抗原肽在 MHC 类 II 和 I 上的交叉呈递分别为 CD4+和 CD8+T 细胞。因此，FcRn 调节配体在不同类型的细胞内和细胞间的运输，还调节免疫细胞中 IgG-ICs 的处理。因此，该受体参与免疫监视和抗感染保护。在这篇简短的综述中，我们强调了造血和非造血细胞表达的 FcRn 如何有助于黏膜屏障的免疫调节——这一生物学可以用于开发生物制剂和亚单位疫苗，以实现非侵入性递药。
