Roundtrip Ticket for Secretory IgA: Role in Mucosal Homeostasis?

Abstract

An important activity of mucosal surfaces is the production of Ab referred to as secretory IgA (SIgA). SIgA serves as the first line of defense against microorganisms through a mechanism called immune exclusion. In addition, SIgA adheres selectively to M cells in intestinal Peyer’s patches, thus mediating the transepithelial transport of the Ab molecule from the intestinal lumen to underlying gut-associated organized lymphoid tissue. In Peyer’s patches, SIgA binds and is internalized by dendritic cells in the subepithelial dome region. When used as carrier for Ags in oral immunization, SIgA induces mucosal and systemic responses associated with production of anti-inflammatory cytokines and limits activation of dendritic cells. In terms of humoral immunity at mucosal surfaces, SIgA appears thus to combine properties of a neutralizing agent (immune exclusion) and of a mucosal immunopotentiator inducing effector immune responses in a noninflammatory context favorable to preserve local homeostasis of the gastrointestinal tract.

Interactions among dendritic cells, macrophages, and epithelial cells in the gut: implications for immune tolerance

“…For instance, commensal reactive IgAs are found in mice reared under specific pathogen-free conditions [47]. These IgAs could be either specific or polyreactive and serve as anchors, which may either prevent internalization or promote a controlled entrance of bacteria via M cells [48]. Gut DCs also have the peculiar capacity to induce T reg cell development; however, there is no systemic tolerance to commensal bacteria.…”

Role of mucosal dendritic cells in inflammatory bowel disease

“…There are different pathways by which luminal antigens can gain access in the lamina propria [48] . In all pathways, mucosal DCs are supposed to play key roles.…”

Dysfunctions of the Iga system: a common link between intestinal and renal diseases

“…In the gut lumen, high-affinity IgA antibodies from T cell-dependent pathways bind to the layer of mucus, prevent the adherence and invasion of pathogenic microorganisms and neutralize pathogen toxins or enzymes. 18 Conversely, low-affinity IgA emerging from T cell-independent pathways sequester commensal bacteria of the intestinal lumen through a process known as 'immune exclusion'. 10 SIgA can inhibit the entry of these bacteria by surrounding pathogens with a hydrophilic shell that is repelled by the mucin glycocalyx at mucosal surfaces.…”

“…Moreover, SIgA can inhibit virus production via intracellular interception of viral antigens during transepithelial IgA transport. 18 In the lamina propria, IgA bind and transport antigens into the lumen via the pIgR at the basolateral side of the epithelial cells by transcytosis or using FcaRIbearing phagocytes. 14 In addition to controlling pathogens and commensals, IgA antibodies inside epithelial cells neutralize microbial products that have proinflammatory activity, such as lipopolysaccharide.…”