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.

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

Objective: Dendritic 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.

Human gut dendritic cells drive aberrant gut-specific t-cell responses in ulcerative colitis, characterized by increased IL-4 production and loss of IL-22 and IFNγ.

: 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.

Altered human gut dendritic cell properties in ulcerative colitis are reversed by Lactobacillus plantarum extracellular encrypted peptide STp.

Scope: The human/microbiota cross-talk is partially mediated by bacteria-derived peptides like Serine-Threonine peptide (STp), which is resistant to gut proteolysis, is found in the human healthy colon and induces regulatory properties on gut dendritic cells (DCs); here we characterized human gut DC in ulcerative colitis (UC) patients and studied the effect of STp on their properties.

Methods And Results: Human colonic DC from healthy controls and UC patients were isolated, conditioned for 24 h +/- STp and characterized by flow cytometry, immunohistochemistry, and electron microscopy. Expression of immature DC markers DC-SIGN and ILT3, and Toll-like receptors were increased on gut UC-DC.

Dysregulated circulating dendritic cell function in ulcerative colitis is partially restored by probiotic strain Lactobacillus casei Shirota.

Background: Dendritic cells regulate immune responses to microbial products and play a key role in ulcerative colitis (UC) pathology. We determined the immunomodulatory effects of probiotic strain Lactobacillus casei Shirota (LcS) on human DC from healthy controls and active UC patients.

Methods: Human blood DC from healthy controls (control-DC) and UC patients (UC-DC) were conditioned with heat-killed LcS and used to stimulate allogeneic T cells in a 5-day mixed leucocyte reaction.

Oral tacrolimus as maintenance therapy for refractory ulcerative colitis--an analysis of outcomes in two London tertiary centres.

Background: The medical management of refractory ulcerative colitis (UC) remains a significant challenge. Two randomised controlled studies have demonstrated tacrolimus therapy is effective for the induction of remission of moderate to severe UC. However, the long term outcomes of UC patients treated with tacrolimus as maintenance therapy are not certain.

Mechanisms of action of anti-tumor necrosis factor α agents in Crohn's disease.

Crohn's disease (CD) is characterized by inflammation that can affect any part of the gastrointestinal tract. It is a chronic destructive condition that follows a relapsing-remitting course and can lead to disability and a poor quality of life. Lifelong pharmacotherapy with systemic immunomodulator therapies remains the cornerstone of CD management.

Intestinal dendritic cells: their role in intestinal inflammation, manipulation by the gut microbiota and differences between mice and men.

The intestinal immune system maintains a delicate balance between immunogenicity against invading pathogens and tolerance of the commensal microbiota and food antigens. Dendritic cells (DC) generate primary T-cell responses, and determine whether these responses are immunogenic or tolerogenic. The regulatory role of DC is of particular importance in the gut due to the high antigenic load.

IL-6 promotes immune responses in human ulcerative colitis and induces a skin-homing phenotype in the dendritic cells and Tcells they stimulate.

Dendritic cells (DCs) control the type and location of immune responses. Ulcerative colitis (UC) is considered a Th2 disease mediated by IL-13 where up to one third of patients can develop extraintestinal manifestations. Colonic biopsies from inflamed and noninflamed areas of UC patients were cultured in vitro and their supernatants were used to condition human blood enriched DCs from healthy controls.

T-cell proliferation and forkhead box P3 expression in human T cells are dependent on T-cell density: physics of a confined space?

T-cell proliferation rates in vitro depend on factors including initial T-cell number, dose of stimulus, culture time, and available physical space. The role of forkhead box P3 (FoxP3) in the identification of T cells with a regulatory phenotype remains controversial in humans. Through 5-carboxyfluorescein diacetate succinimidyl ester labeling of human T cells and subsequent culture of different numbers of T cells and antigen-presenting cells (APC), we studied proliferative T-cell responses and FoxP3 expression in divided T cells.

A dangerous combination of binge and purge.

We present a 36-year-old female diagnosed with Crohn's disease at the age of 11 years. In 2001, she underwent a total colectomy and further small bowel resection as a result of active Crohn's. Her residual anatomy consisted of 150 cm of small bowel to an end jejunostomy.

H1N1 vaccines in a large observational cohort of patients with inflammatory bowel disease treated with immunomodulators and biological therapy.

Background: Safety data are lacking on influenza vaccination in general and on A (H1N1)v vaccination in particular in patients with inflammatory bowel disease (IBD) receiving immmunomodulators and/or biological therapy.

Aims And Methods: The authors conducted a multicentre observational cohort study to evaluate symptoms associated with influenza H1N1 adjuvanted (Pandemrix, Focetria, FluvalP) and non-adjuvanted (Celvapan) vaccines and to assess the risk of flare of IBD after vaccination. Patients with stable IBD treated with immunomodulators and/or biological therapy were recruited from November 2009 until March 2010 in 12 European countries.

Skin lesions with sinister associations.

Many serious diseases declare their presence with dermatological features. These include rashes, pigmentation changes, vasculitic lesions and on occasions highly characteristic skin lesions. This article describes a case of Sweet's syndrome which demonstrated typical skin lesions, and discusses the presentation, management and frequent sinister associations of this syndrome.

Atrial fibrillation-related cardiomyopathy: a case report.

Sustained chronic tachyarrhythmias often cause a deterioration of cardiac function known as tachycardia-induced cardiomyopathy or tachycardiomyopathy.The incidence of tachycardia-induced cardiomyopathy is unknown, but in selected studies of patients with atrial fibrillation, approximately 25% to 50% of those with left ventricular dysfunction had some degree of tachycardia-induced cardiomyopathy. It is an important clinical entity due to the high incidence and potential reversibility of the disease process.