IL-22 is mainly produced at barrier surfaces by T cells and innate lymphoid cells and is crucial to maintain epithelial integrity. However, dysregulated IL-22 action leads to deleterious inflammation and is involved in diseases such as psoriasis, intestinal inflammation and cancer. IL-22BP is a soluble inhibitory IL-22 receptor and may represent a crucial regulator of IL-22. We show both in rats and mice that, in the steady state, the main source of IL-22BP is constituted by a subset of conventional dendritic cells (DC) in lymphoid and non lymphoid tissues. In mouse intestine, IL-22BP was specifically expressed in lamina propria CD103+CD11b+ DC. In humans, IL-22BP was expressed in immature monocyte-derived DC (MDDC) and strongly induced by retinoic acid (RA) but dramatically reduced upon maturation. Our data suggest that a subset of immature DC may actively participate in the regulation of IL-22 activity in the gut by producing high levels of IL-22BP.

Cross-presentation of cellular antigens is crucial for priming CD8+ T cells, and generating immunity to intracellular pathogens—particularly viruses. It is unclear which intestinal phagocytes perform this function in vivo. To address this, we examined dendritic cells (DCs) from the intestinal lymph of IFABP-tOVA 232-4 mice, which express ovalbumin in small intestinal epithelial cells (IECs). Among lymph DCs (LDCs) only CD103+ CD11b− CD8α+ DCs cross-present IEC-derived ovalbumin to CD8+ OT-I T cells. Similarly, in the mesenteric lymph nodes (MLNs), cross-presentation of IEC–ovalbumin was limited to the CD11c+ MHCIIhi CD8α+ migratory DCs, but absent from all other subsets, including the resident CD8αhi DCs. Crucially, delivery of purified CD8α+ LDCs, but not other LDC subsets, into the MLN subcapsular lymphatic sinus induced proliferation of ovalbumin-specific, gut-tropic CD8+ T cells in vivo. Finally, in 232-4 mice treated with R848, CD8α+ LDCs were uniquely able to cross-prime interferon γ-producing CD8+ T cells and drive their migration to the intestine. Our results clearly demonstrate that migrating CD8α+ intestinal DCs are indispensable for cross-presentation of cellular antigens and, in conditions of inflammation, for the initial differentiation of effector CD8+ T cells. They may therefore represent an important target for the development of antiviral vaccinations.

Objective. In rats transgenic for human HLA-B27 and ␤ 2 -microglobulin (B27-transgenic rats), colitis and peripheral inflammation develop spontaneously. Therefore, B27-transgenic rats provide a model of spondylarthritis. Because inflammation in these rats requires CD4؉ T lymphocytes and involves intestinal pathology, we hypothesized that dendritic cells (DCs) that migrate from the intestine and control CD4؉ T cell differentiation would be aberrant in B27-transgenic rats.Methods. Migrating intestinal lymph DCs were collected via thoracic duct cannulation from B27-transgenic and control (HLA-B7-transgenic or nontransgenic) rats. The phenotypes of these DCs and of mesenteric lymph node DCs were assessed by flow cytometry. The ability of DCs to differentiate from bone marrow precursors in vitro was also assessed.Results. Lymph DCs showed increased activation and, strikingly, lacked the specific DC population that is important for maintaining tolerance to self-antigens. This population of DCs was also depleted from the mesenteric lymph nodes of B27-transgenic rats. Furthermore, in vitro culture of DCs from bone marrow precursors revealed a defect in the ability of B27-transgenic rats to produce DCs of the migratory phenotype, although the DCs that were generated induced enhanced interleukin-17 (IL-17) production from naive CD4؉ T cells. Conclusion.We describe 2 different mechanisms by which HLA-B27 may contribute to inflammatory disease: increased apoptotic death of B27-transgenic DCs that normally function to maintain immunologic tolerance and enhanced IL-17 production from CD4؉ T cells stimulated by the surviving B27-transgenic DCs.

Salmonella infection is a globally important cause of gastroenteritis and systemic disease, and is a useful tool to study immune responses in the intestine. Although mechanisms leading to immune responses against Salmonella have been extensively studied, questions remain about how bacteria travel from the intestinal mucosa to the mesenteric lymph nodes (MLN), a key site for antigen presentation. Here, we used a mouse model of infection with Salmonella enterica serovar Typhimurium (STM) to identify changes in intestinal immune cells induced during early infection. We then used fluorescently-labelled STM to identify interactions with immune cells, from the site of infection, through migration in lymph, to the MLN. We show that viable STM can be carried in the lymph by any subset of migrating dendritic cells, but not by macrophages. Moreover, approximately half of the STM in lymph are not associated with cells at all, and travel autonomously. Within the MLN, STM associates with dendritic cells and B cells, but predominantly with MLN-resident macrophages. In conclusion, we describe the routes used by STM to spread systemically in the period immediately after infection. This deeper understanding of the infection process could open new avenues for controlling it.

Surface expression of HD6-reactive B27 molecules on B27-TG rat splenocytes is consistent with a pathogenic role for NC-B27 in SpA. Interaction of NC-B27 with innate immune receptors could be critical in SpA pathogenesis, and we show that this may be influenced by the availability and composition of the B27-binding peptide pool.