Adaptive Immune Regulation in the Gut: T Cell–Dependent and T Cell–Independent IgA Synthesis

Abstract

In mammals, the gastrointestinal tract harbors an extraordinarily dense and complex community of microorganisms. The gut microbiota provide strong selective pressure to the host to evolve adaptive immune responses required for the maintenance of local and systemic homeostasis. The continuous antigenic presence in the gut imposes a dynamic remodeling of gut-associated lymphoid tissues (GALT) and the selection of multiple layered strategies for immunoglobulin (Ig) A production. The composite and dynamic gut environment also necessitates heterogeneous, versatile, and convertible T cells, capable of inhibiting (Foxp3(+) T cells) or helping (T(FH) cells) local immune responses. In this review, we describe recent advances in our understanding of dynamic pathways that lead to IgA synthesis, in gut follicular structures and in extrafollicular sites, by T cell-dependent and T cell-independent mechanisms. We discuss the finely tuned regulatory mechanisms for IgA production and emphasize the role of mucosal IgA in the selection and maintenance of the appropriate microbial composition that is necessary for immune homeostasis.

The M Cell-Targeting Ligand Promotes Antigen Delivery and Induces Antigen-Specific Immune Responses in Mucosal Vaccination

“…Application of vaccines through an oral mucosal route is an ideal vaccination strategy because it induces effective protective immunity through eliciting Ag-specific IgA Ab production in mucosal tissue, a major site of pathogen infection, and simultaneously through assisting the induction of Ag-specific systemic immune responses (40,41). Because a single epithelial layer of mucosa protects the host from pathogenic invasion through tight regulation of luminal access and surveillance and because the mucosal environment induces tolerogenic immunity against the introduced Ag, development of an effective mucosal adjuvant that can stimulate the immune system and deliver Ag is critical for mucosal vaccine development.…”

“…4). In particular, lymphocytes from PPs, a mucosal inductive site, were found to secrete IL-4, IL-5, and IL-6; these cytokines are known to be associated with isotype switching to secretory IgA through an autocrine TGF-b1-dependent loop and with overcoming oral tolerance environments (40,60). It is possible that by targeting M cells immune tolerance rather than immune stimulation may be induced.…”

Re-thinking the functions of IgA+plasma cells

“…On the other hand, PP and MLN can support both TD as well as TI IgA induction. [27][28][29] Several CD4 C T cell subsets have been implicated in germinal center (GC)-driven IgA responses including T-regulatory cells (Treg), 30 T-follicular helper cells (T FH ) 31 and Th17 cells. 32,33 It is likely that the generation of IgA C PC depends on the nature of the Ag and the location of where B cells are primed.…”

Effect of Minerals on Intestinal IgA Production Using Deep Sea Water Drinks

“…Intestinal IgA plays a crucial role in maintaining host-gut flora homeostasis, and is mostly produced T cell-dependently in Peyer's patch germinal centers. 4) Probiotics, vitamins, minerals, and other components are thought to be involved in the maintenance of intestinal immune balance homeostasis. 5) Aside from the intestinal immune system, general health maintenance in humans is greatly influenced by minerals.…”