Compartment-specific immunity in the human gut: properties and functions of dendritic cells in the colon versus the ileum

Abstract

ObjectiveDendritic cells (DC) mediate intestinal immune tolerance. Despite striking differences between the colon and the ileum both in function and bacterial load, few studies distinguish between properties of immune cells in these compartments. Furthermore, information of gut DC in humans is scarce. We aimed to characterise human colonic versus ileal DC.DesignHuman DC from paired colonic and ileal samples were characterised by flow cytometry, electron microscopy or used to stimulate T cell responses in a mixed leucocyte reaction.ResultsA lower proportion of colonic DC produced pro-inflammatory cytokines (tumour necrosis factor-α and interleukin (IL)-1β) compared with their ileal counterparts and exhibited an enhanced ability to generate CD4+FoxP3+IL-10+ (regulatory) T cells. There were enhanced proportions of CD103+Sirpα− DC in the colon, with increased proportions of CD103+Sirpα+ DC in the ileum. A greater proportion of colonic DC subsets analysed expressed the lymph-node-homing marker CCR7, alongside enhanced endocytic capacity, which was most striking in CD103+Sirpα+ DC. Expression of the inhibitory receptor ILT3 was enhanced on colonic DC. Interestingly, endocytic capacity was associated with CD103+ DC, in particular CD103+Sirpα+ DC. However, expression of ILT3 was associated with CD103− DC. Colonic and ileal DC differentially expressed skin-homing marker CCR4 and small-bowel-homing marker CCR9, respectively, and this corresponded to their ability to imprint these homing markers on T cells.ConclusionsThe regulatory properties of colonic DC may represent an evolutionary adaptation to the greater bacterial load in the colon. The colon and the ileum should be regarded as separate entities, each comprising DC with distinct roles in mucosal immunity and imprinting.

Age-associated modifications of intestinal permeability and innate immunity in human small intestine

“…Alternatively, this might be linked to intrinsic differences between distinct areas of the intestine, such as the colon and terminal ileum. The latter hypothesis is supported by the recent observation that in humans the regulatory features of DCs varied according to their geographical location in the gut (27). Thus, it is possible that while terminal ileum DCs are characterized by increased production of IL-6 in ageing, DCs located in the large intestine may display a different array of age-related modifications that might lead to a more significant alteration of the local inflammatory status and intestinal permeability.…”

Characterization of candidate genes in inflammatory bowel disease–associated risk loci

“…To further confirm this enrichment, we directly compared the number of significantly upregulated or downregulated genes in both data sets and found that 51 of our signature genes (26 upregulated and 25 downregulated) were also significantly regulated in the independent set ( P = 0.0045 and P = 0.0013, respectively; hypergeometric test). This differential expression analysis of IBD-associated genes between TI and colon identifies tissue-specific marker genes and can inform hypotheses to further characterize distinctions observed between the TI and colon (17, 18). …”

Tissue Microenvironments in the Nasal Epithelium of Rainbow Trout (Oncorhynchus mykiss) Define Two Distinct CD8α+ Cell Populations and Establish Regional Immunity

“…In this respect, the expression of MHC-II is also variable in different regions of the intestine (5, 13) and professional APCs in mammals have compartment-specific properties (2, 5, 14). Importantly, epithelial cells, despite not being considered professional APCs, express MHC-II (15–17) and the levels and patterns of expression change under pathological conditions (18, 19).…”