Secretory IgA in Intestinal Mucosal Secretions as an Adaptive Barrier against Microbial Cells

Abstract

Secretory IgA (SIgA) is the dominant antibody class in mucosal secretions. The majority of plasma cells producing IgA are located within mucosal membranes lining the intestines. SIgA protects against the adhesion of pathogens and their penetration into the intestinal barrier. Moreover, SIgA regulates gut microbiota composition and provides intestinal homeostasis. In this review, we present mechanisms of SIgA generation: T cell-dependent and -independent; in different non-organized and organized lymphoid structures in intestinal lamina propria (i.e., Peyer's patches and isolated lymphoid follicles). We also summarize recent advances in understanding of SIgA functions in intestinal mucosal secretions with focus on its role in regulating gut microbiota composition and generation of tolerogenic responses toward its members.

Keywords: gut; immune homeostasis; microbiota; mucosal secretions; secretory immunoglobulin A; tolerance.

Figure 1

Schematic illustration of T cell-dependent (TD) and -independent (TI) regulation of secretory class A immunoglobulin (SIgA) production in intestinal epithelium (IE) underlying organized structures: (a) Peyer’s patches (PPs) and (b) isolated lymphoid follicles (ILFs) and (c) nonorganized regions (NORs) located in intestinal lamina propria (LP). Signaling pathways between immune and non-immune cells: microfold epithelial cell (M), goblet cell (G), epithelial cell/enterocyte (EC), dendritic cell (DC), follicular dendritic cell (FDC), stromal cell (StC), several types of T cells including: naïve CD4⁺ T cell (CD4⁺ T), follicular helper T cell (T_FH), regulatory T cell (Treg), and B cells (B) including: primitive B1 and conventional B2 cells, plasma cell (PC), involving signaling molecules: class II major histocompatibility complex (MHC), T cell receptor (TCR), cluster of differentiation 40 (CD40), CD40 ligand (CD40L), interleukin (IL)-21, IL-6, IL-10, transforming growth factor beta 1 (TGFβ), activation-induced cytidine-deaminase (AID), Toll-like receptor (TLR), thymic stromal lymphopoietin (TSLP), a proliferation-inducing ligand (APRIL), B-cell-activating factor of the TNF family (BAFF), C-X-C motif chemokine ligand 13 (CXCL13), C-X-C motif chemokine receptor 5 (CXCR5), nitric oxide (NO) in response to bacterial antigens derived from intestinal microbiota (IM) lead to class-switch recombination (CSR) and somatic hypermutation (SHM) within immunoglobulin loci of B cells followed by production of specific membrane bound immunoglobulins (IgM, IgA) and secretory immunoglobulins (SIgA) within lamina propria and transcytosed via polymeric immunoglobulin receptor (pIgR) by enterocytes to intestinal lumen (IL); mucus layer (ML). Detailed description in text.