Introduction to Dendritic Cells
Dendritic cells (DCs) play an important role in the gut as a specialized class of antigen-presenting cells with the dual function of inducing self-antigen tolerance and non-self-antigen immunity. DCs in the intestine are predominantly distributed beneath the epithelial cell monolayer, and they detect antigens in the intestinal lumen, including commensal bacteria, dietary antigens, and damaged epithelial cell-associated components to monitor the intestinal luminal environment. At homeostasis, intestinal DCs appear to be tolerant. Indeed, intestinal DCs ingesting orally given antigens or epithelial apoptosis products migrate to draining mesenteric lymph nodes (MLNs) to suppress immune responses to these antigens by inducing CD4+Foxp3+ regulatory T cells (Tregs). In addition, intestinal DCs carrying live commensal bacteria induce IgA class switching in B cells upon arrival at MLNs. Thus, DCs play an important role in maintaining intestinal homeostasis by transporting antigens from the intestinal lumen to the draining lymph nodes.
Dendritic Cells Promote IgA Production
There is growing evidence suggesting that the induction of IgA relies heavily on signals from the intestinal environment, which consists of commensal bacteria and dietary compounds. DCs present in the intestinal mucosa are strategically positioned to sample antigens and microorganisms from the gut lumen, thus serving as a bridge between the external environment and the immune system. It has been suggested that some subtypes of DCs could promote the IgA production by B cells. For example, a specific subset of DCs in Peyer's patches can produce retinoic acid, which aids the differentiation of B cells into IgA-producing plasma cells. Moreover, these DCs could induce the expression of gut-homing receptors on B cells, consequently guiding these cells to the intestine where they differentiate into IgA-producing cells under the influence of transforming growth factor-beta (TGF-β). Furthermore, DCs can also stimulate IgA production by promoting the generation of T follicular helper (Tfh) cells, a subset of CD4+ T cells that provide help to B cells for the production of high-affinity antibodies. DCs present in the germinal centers can provide essential survival signals to Tfh cells, and at the same time, these DCs can receive B cell help signals. DCs also interact extensively with the gut microbiota, which can influence IgA production. Complex microbial communities are involved in the stimulation of DCs, which enhances the differentiation of B cells into IgA-producing cells in turn. Moreover, recent studies have shown that certain bacteria can selectively stimulate DCs to promote IgA responses.
Fig 1. Dendritic cells promote IgA production.1
Cellular Interactions Influence the Activity of Dendritic Cells
In the human body, a complex interaction occurs within the gut as DCs intertwine with other cells to control the production of IgA. Both intestinal epithelial cells (IECs) and intestinal mesenchymal stromal cells (SCs) modulate DC functions through various cytokines and signaling molecules. And, the molecules produced by IECs, such as type I interferons and nitric oxide, and factors (e.g., BAFF and APRIL) generated by SCs, all interact to influence the DC functions and the IgA production. Moreover, the interaction and collaboration among DCs, B cells, and other immune cells within the gut are integral to the production of IgA.
To sum up, DCs are instrumental to the synthesis of IgA and preserving intestinal immunity. They achieve this by transporting antigens, steering the functionality of immune cells, and interacting with other cell types within the gut. A deeper appreciation of the process of DCs-mediated IgA production could pave the way for novel strategies to boost mucosal immunity and tackle intestinal diseases.
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Reference
- Tezuka, Hiroyuki, and Toshiaki Ohteki. "Regulation of IgA production by intestinal dendritic cells and related cells." Frontiers in immunology 10 (2019): 1891.
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