The Polymeric Immunoglobulin Receptor

Abstract

Secretory Immunoglobulin A (SIgA) antibodies represent the first line of antigen‐specific immune defence protecting the mucosal surfaces against environmental pathogens and antigens and maintaining homoeostasis with the commensal microbiota. The polymeric Ig receptor (pIgR) plays the dual role of transporting locally produced dimeric IgA across mucosal epithelia and serving as the precursor of the secretory component moiety of SIgA. The complex regulation of pIgR expression and transcytosis by host and microbial factors is finely tuned to optimise the role of SIgA in mucosal immunity. Recent discoveries highlight the dynamic cross‐talk between pIgR, SIgA and the commensal microbiota that populate our mucosal surfaces. Dysregulation of pIgR expression and/or function can result in profound consequences for the pathogenesis of infectious, inflammatory and neoplastic diseases. Future research into the function and regulation of pIgR and SIgA may offer new insights into the prevention and treatment of diseases that originate at mucosal surfaces. Key Concepts: Secretory IgA (SIgA) antibodies represent the first line of antigen‐specific immune defence at mucosal surfaces. The polymeric immunoglobulin receptor (pIgR) transports dimeric IgA across mucosal epithelial cells and serves as the precursor for the secretory component of SIgA. Transcription of the PIGR gene in mucosal epithelial cells is regulated by signalling pathways initiated by host cytokines and microbial factors, involving the cytoplasmic adapter protein, myeloid differentiation primary response protein 88 (MyD88). SIgA mediates immune protection by immune exclusion, intracellular neutralisation of antigens and pathogens and excretion of IgA‐containing immune complexes by pIgR‐mediated epithelial transcytosis. Cross‐talk between pIgR, SIgA and commensal bacteria regulates the composition of the gut microbiota and promotes intestinal homoeostasis. Dysregulated expression or function of pIgR can contribute to the pathology of infectious, inflammatory and neoplastic diseases.

Coevolution of Mucosal Immunoglobulins and the Polymeric Immunoglobulin Receptor: Evidence That the Commensal Microbiota Provided the Driving Force

“…The pIgR is expressed on the surface of glandular and mucosal epithelial binds, where it binds selectively to polymeric Ig (pIg) and mediates its transport across epithelial cells into external secretions (reviewed in [17,111,112] our knowledge of pIgR-mediated transcytosis of mucosal Igs is derived from studies of mammalian secretory IgA (SIgA), as illustrated in Figure 4. Transcription of the PIGR gene and translation of pIgR mRNA is accompanied by insertion of the nascent protein into the endoplasmic reticulum.…”

“…The early emergence of pIgR in vertebrate evolution provided a mechanism for efficient transport of mucosal Igs into external secretions. It is well documented that crosstalk between mucosal epithelial cells and the resident microbiota modulates expression of pIgR (reviewed in [17,111,112]), and it is reasonable to assume that these host-microbe interactions provided a driving force for evolution of the PIGR gene in vertebrates. The first demonstration that gut bacteria may modulate pIgR expression in epithelial cells was the finding that butyrate, a bacterial fermentation product and important energy source in the colon, upregulated expression of pIgR in the human colonic epithelial cell line HT-29 [146].…”

Lessons from mother: Long-term impact of antibodies in breast milk on the gut microbiota and intestinal immune system of breastfed offspring

“…The predominant type of antibody in breast milk is secretory (S)IgA, which is transported across mammary gland epithelial cells by the polymeric immunoglobulin receptor (pIgR). 12 At the apical surface, proteolytic cleavage releases SIgA, in which IgA is covalently attached to secretory component (SC), the extracellular domain of pIgR. The SC moiety of SIgA protects SIgA from degradation by host and microbial proteases and provides additional innate immune functions.…”

Preparation of the porcine secretory component and a monoclonal antibody against this protein

“…To enter external secretions, locally synthesized IgA is transported across glandular and mucosal epithelial cells, and this process is mediated by covalent binding of IgA to pIgR [7][8][9]. The pIgR-pIgA complex is transcytosed across the cell, and pIgR is then cleaved by a protease within a 42-amino acid region adjacent to the cell membrane at the luminal surface.…”