Dendritic cell functions in the inductive and effector sites of intestinal immunity

Abstract

The intestine is constantly exposed to foreign antigens, which are mostly innocuous but can sometimes be harmful. Therefore, the intestinal immune system has the delicate task of maintaining immune tolerance to harmless food antigens while inducing tailored immune responses to pathogens and regulating but tolerating the microbiota. Intestinal dendritic cells (DCs) play a central role in these functions as sentinel cells able to prime and polarize the T cell responses. DCs are deployed throughout the intestinal mucosa but with local specializations along the gut length and between the diffuse effector sites of the gut lamina propria (LP) and the wellorganized immune inductive sites comprising isolated lymphoid follicles (ILFs), Peyer's patches (PPs), and other species-specific gutassociated lymphoid tissues (GALTs). Understanding the specificities of each intestinal DC subset, how environmental factors influence DC functions, and how these can be modulated is key to harnessing the therapeutic potential of mucosal adaptive immune responses, whether by enhancing the efficacy of mucosal vaccines or by increasing tolerogenic responses in inflammatory disorders. In this review, we summarize recent findings related to intestinal DCs in steady state and upon inflammation, with a special focus on their functional specializations, highly dependent on their microenvironment.

Neonatal Peyer’s patch cDC activation as a pacemaker of postnatal immune maturation

“…Interestingly, the total phagocyte density was not different between the neonatal (PND5, PND11), weanling (PND21) and adult PP (Figure 2A, Figure S2A). Next, we subjected MNP from neonatal, weanling and adult mice to flow cytometry (PND11, PND21, adult) and scRNAseq (PND11, adult) aiming to characterize the subset composition and transcriptional profile of the various MNP subsets found in PP (Figures S2B, S2C, 2B and 2C) (Bonnardel et al, 2017; Luciani et al, 2021). Whereas the adult MNP compartment was dominated by cDC2 (SIRPa +/hi BST2 - XCR1 - MHCII + CD11c + ) they were significantly reduced in neonatal PP.…”

“…subjected MNP from neonatal, weanling and adult mice to flow cytometry (PND11, PND21, (Bonnardel et al, 2017;Luciani et al, 2021).…”

“…ns, not significant; *, p<0.05; ** p<0.01; *** p<0.001; ****, p<0.0001. (Bonnardel et al, 2017;Luciani et al, 2021).…”

“…PP lack afferent lymphatics but instead sample antigen directly from the small intestinal lumen. In the adult host, an array of conventional and monocyte-derived dendritic cells organized in an intricate microarchitecture positioned between subepithelial dome (SED) and interfollicular regions (IFR) then prime T cells (Luciani et al, 2021).…”

Rewiring host–microbe interactions and barrier function during gastrointestinal inflammation

“…The inductive sites comprise the mesenteric lymph nodes (mLNs) and gut-associated lymphoid tissues (GALT), where the latter include Peyer’s patches, the cecal patch, colonic patches, isolated lymphoid follicles, and immature cryptopatches (in the mouse) [ 24 ]. The different lymphoid tissues of the gut perform specialized but overlapping functions in relation to regulating tolerance vs immune activation [ 25 ]. While numerous checkpoints are in place to ensure well-balanced immunity, a key effector arm relates to the substantial amounts of transforming growth factor β (TGFβ) produced by the epithelium.…”