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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.

The pathogenesis of inflammatory bowel disease is incompletely understood but results from a dysregulated intestinal immune response to the luminal microbiota. CD4+ T cells mediate tissue injury in the inflammatory bowel disease–associated immune response. Dendritic cells (DC) generate primary T-cell responses and mediate intestinal immune tolerance to prevent overt inflammation in response to the gut microbiota. However, most information regarding function of intestinal DC has come from mouse models, and information in humans is scarce. We show here that intestinal DC subsets are skewed in ulcerative colitis (UC) in humans, with a loss of CD103+ lymph-node homing DC; this intestinal DC subset preferentially generates regulatory T cells in mice. We show infiltrates of DC negative for myeloid marker CD11c, with enhanced expression of Toll-like receptors for bacterial recognition. After mixed leukocyte reaction, DC from the inflamed UC colon had an enhanced ability to generate gut-specific CD4+ T cells with enhanced production of interleukin-4 but a loss of interferon γ and interleukin-22 production. Conditioning intestinal DC with probiotic strain Lactobacillus casei Shirota in UC partially restored their normal function indicated by reduced Toll-like receptor 2/4 expression and restoration of their ability to imprint homing molecules on T cells and to generate interleukin-22 production by stimulated T cells. This study suggests that T-cell dysfunction in UC is driven by DC. T-cell responses can be manipulated indirectly through effects of bacterial conditioning on gut DC with implications for immunomodulatory effects of the commensal microbiota in vivo. Manipulation of DC to allow generation of DC-specific therapy may be beneficial in inflammatory bowel disease.

[Serra Tumay] took a long crossing pass from Gina Wideroff and, after outracing two defenders, drilled a low liner into the left corner of the net at the 47-minute mark. Five minutes later, Tumay broke through the middle and in full stride finished a header from Emily Brockway to put St. Andrew's ahead 2-0.

Class 3A: St. Andrew's (16-2-0) at Bishop Verot (12-7-2); Gulliver Prep (16-2-1) at Pine Crest (11-5-5); Archbishop Carroll (15-4-1) at American Heritage (22-0-1).

Junior quarterback [Hawkins] threw TD passes of 24, 46 and 23 yards to [Darrell Madry] as the Bulldogs (1-0) took a 21-7 halftime lead. Coral Springs (0-2) had jumped out to an early 7-0 lead on a 2-yard quarterback keeper by Mike Garrity with 7:44 remaining in the first period, but it was all South Broward after that as the Bulldogs scored 28 unanswered points.

The 3.30am police raids were sparked after officers in the UK allegedly discovered communication between a 14-year-old Blackburn boy and Mr Besim, which led authorities to believe there could be an imminent attack with \"edged weapons\".

POLICE say they smashed a sophisticated multi-million-dollar heroin trafficking ring in co-ordinated dawn raids across Melbourne yesterday.

POLICE say they smashed a sophisticated multi-million-dollar heroin trafficking ring in co-ordinated dawn raids across Melbourne yesterday.