Chemokine (C-C Motif) Receptor 2 Mediates Dendritic Cell Recruitment to the Human Colon but Is Not Responsible for Differences Observed in Dendritic Cell Subsets, Phenotype, and Function Between the Proximal and Distal Colon.

BACKGROUND & AIMS: Most knowledge about gastrointestinal (GI)-tract dendritic cells (DC) relies on murine studies where CD103+ DC specialize in generating immune tolerance with the functionality of CD11b+/- subsets being unclear. Information about human GI-DC is scarce, especially regarding regional specifications. Here, we characterized human DC properties throughout the human colon. METHODS: Paired proximal (right/ascending) and distal (left/descending) human colonic biopsies from 95 healthy subjects were taken; DC were assessed by flow cytometry and microbiota composition assessed by 16S rRNA gene sequencing. RESULTS: Colonic DC identified were myeloid (mDC, CD11c+CD123-) and further divided based on CD103 and SIRPα (human analog of murine CD11b) expression. CD103-SIRPα+ DC were the major population and with CD103+SIRPα+ DC were CD1c+ILT3+CCR2+ (although CCR2 was not expressed on all CD103+SIRPα+ DC). CD103+SIRPα- DC constituted a minor subset that were CD141+ILT3-CCR2-. Proximal colon samples had higher total DC counts and fewer CD103+SIRPα+ cells. Proximal colon DC were more mature than distal DC with higher stimulatory capacity for CD4+CD45RA+ T-cells. However, DC and DC-invoked T-cell expression of mucosal homing markers (β7, CCR9) was lower for proximal DC. CCR2 was expressed on circulating CD1c+, but not CD141+ mDC, and mediated DC recruitment by colonic culture supernatants in transwell assays. Proximal colon DC produced higher levels of cytokines. Mucosal microbiota profiling showed a lower microbiota load in the proximal colon, but with no differences in microbiota composition between compartments. CONCLUSIONS: Proximal colonic DC subsets differ from those in distal colon and are more mature. Targeted immunotherapy using DC in T-cell mediated GI tract inflammation may therefore need to reflect this immune compartmentalization

A GPI-linked isoform of the IgD receptor regulates resting B cell activation

The induction of a humoral response depends upon efficient cross-linking by antigen of surface immunoglobulin on primary B lymphocytes. We demonstrate here the presence of a glycosylphosphatidylinositol-linked isoform of membrane IgD (mIgD) receptors on murine resting B cells. This subset was constitutively localized to cell membrane raft microdomains. Its stimulation resulted in the activation of cAMP-dependent signaling pathways, which integrated with signals derived from the transmembrane mIgD receptors. This, in turn, provided a mechanism by which the activation status of the target cells could be variably regulated. Thus, by partitioning receptor activity, preimmune B cells can moderate the extent to which they are activated, depending upon the strength of the antigenic stimulus

High fat diet induces anti-inflammatory effect in experimental colitis

357-363The prevalence of ulcerative colitis, one of the inflammatory bowel diseases, has been increasing worldwide. Though fatty diet leads to development of colitis, only little is known about the separate and combined effects of different fat compositions and intermittent fasting, and the effects of preventative dietary changes on experimental colitis. In this study, we investigated the effect of feeding type and frequency on the inflammation ulcerative colitis. Five groups, each comprising 7 male Wistar albino rats, were formed viz. Colitis (as a control), High sucrose diet + Colitis, High sucrose diet + Intermittent fasting + Colitis, High fat diet + Colitis, High fat diet + Intermittent fasting + Colitis. The intermittent fasting group (experimental group) was not fed for 2 days (non-consecutive) in a week (except water), otherwise fed with ad libitum. Following the 7-wk feeding application, the rats were treated with intrarectal administration of 4% acetic acid (pH 2.4). After the rats were sacrificed, the levels of interleukin-1β, insulin, C-reactive protein, leptin, tumor necrosis factor-α, interleukin-6, insulin-like growth factor-1 and adiponectin were analyzed from the blood samples. Analyzes of results revealed a statistically significant decrease in interleukin-1β, C-reactive protein, tumor necrosis factor-α, interleukin-6 and adiponectin levels in High sucrose diet + Intermittent fasting + Colitis and High fat diet + Intermittent fasting + Colitis groups (P<0.05). According to these findings, the amount of fat and fatty acid composition in the fatty diet may have a protective effect against the development of colitis. Intermittent fasting further enhances this protective effect by lowering proinflammatory cytokine levels and reducing systemic inflammation in the body