1. The neonatal Fc receptor in mucosal immune regulation
- Author
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Jeannette Nilsen, Inger Sandlie, Aina Karen Anthi, Kristin Hovden Aaen, Jan Terje Andersen, and Simone Mester
- Subjects
CD4-Positive T-Lymphocytes ,0301 basic medicine ,Immunology ,Antigen presentation ,Antigen-Antibody Complex ,Receptors, Fc ,CD8-Positive T-Lymphocytes ,Biology ,Immunoglobulin G ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Neonatal Fc receptor ,Antigen ,Animals ,Humans ,Immunologic Factors ,Antigens ,Receptor ,Antigen Presentation ,MHC class II ,Mucous Membrane ,Histocompatibility Antigens Class I ,General Medicine ,Cell biology ,030104 developmental biology ,biology.protein ,CD8 ,030215 immunology - Abstract
The neonatal Fc receptor (FcRn) was first recognized for its role in transfer of maternal IgG to the fetus 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.
- Published
- 2021