Medical Management of Inflammatory Bowel Disease.

The past few decades have seen significant advancements in the medical management of both ulcerative colitis (UC) and Crohn's disease (CD). The previous dependence on steroids is no longer an acceptable strategy following the Food and Drug Administration approval for several new classes of medication. These medications include aminosalicylates, immunomodulators, biologics, and oral targeted small-molecule inhibitors.

Vedolizumab Efficacy Is Associated With Decreased Intracolonic Dendritic Cells, Not Memory T Cells.

Background: Vedolizumab, an antibody blocking integrin α4β7, is a safe and effective therapy for Crohn's disease and ulcerative colitis. Blocking α4β7 from binding its cognate addressin MAdCAM-1 on intestinal blood vessel endothelial cells prevents T cells from migrating to the gut mucosa in animal models. However, data supporting this mechanism of action in humans is limited.

Nurse-Administered Propofol Continuous Infusion Sedation: A New Paradigm for Gastrointestinal Procedural Sedation.

Introduction: Nurse-Administered Propofol Continuous Infusion Sedation (NAPCIS) is a new nonanesthesia propofol delivery method for gastrointestinal endoscopy. NAPCIS is adopted from the computer-assisted propofol sedation (CAPS) protocol. We evaluated the effectiveness, efficiency, and safety of NAPCIS in low-risk subjects.

Usefulness of Fluoroscopy for Endoscopic Balloon Dilation of Crohn's Disease-Related Strictures.

Background: Fluoroscopy is often used for endoscopic balloon dilation (EBD) of Crohn's disease (CD)-related strictures. However, its benefit remains unclear.

Aims: To compare EBD with (EBDF) and without (EBDNF) fluoroscopic guidance in CD patients with strictures.

Nurse-Administered Propofol Continuous Infusion Sedation for Gastrointestinal Endoscopy in Patients Who Are Difficult to Sedate.

Background & Aims: Patients who chronically use alcohol, marijuana, or opioids, or suffer from post-traumatic stress disorder (PTSD), can be difficult to sedate with midazolam and fentanyl, and often are referred for monitored anesthesia care during endoscopy. Nurse-administered propofol continuous infusion sedation (NAPCIS), which confers the benefit of propofol-based sedation without the added expense of anesthesia, is effective and safe for sedation of healthy patients. We investigated whether NAPCIS also is effective for patients who are difficult to sedate.

Escherichiacoli-Specific CD4+ T Cells Have Public T-Cell Receptors and Low Interleukin 10 Production in Crohn's Disease.

Background & Aims: Crohn's disease (CD) likely represents decreased immune tolerance to intestinal bacterial antigens. Most CD patients have high titers of antibodies to intestinal commensal proteins, including the outer membrane porin C (OmpC) of Escherichia coli.

Methods: By using major histocompatibility complex II tetramers, we identified an HLA-DRB1∗15:01-restricted peptide epitope of OmpC recognized by CD4+ T cells in peripheral blood mononuclear cells from HLA-DRB1∗15:01+ healthy control (HC) and CD patients.

Immunologic Alterations Associated With Oral Delivery of Anti-CD3 (OKT3) Monoclonal Antibodies in Patients With Moderate-to-Severe Ulcerative Colitis.

Aim: The aim of this study was to determine the immunologic effects and safety of oral anti-CD3 in patients with ulcerative colitis (UC).

Methods: An open-label pilot study of orally delivered anti-CD3 was performed in patients with moderate-to-severe UC. The primary end points were changes in immunologic parameters and evaluation for safety.

Identification of Candidate Biomarkers Associated with Response to Vedolizumab in Inflammatory Bowel Disease.

Background/aims: Vedolizumab is an anti-α4β7 monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). This exploratory study aimed to identify biomarkers associated with vedolizumab response.

Methods: Twenty-six IBD patients (15 with Crohn's, 11 with ulcerative or indeterminate colitis) initiating vedolizumab at a single center between 2014 and 2016 underwent sampling of serum and peripheral blood mononuclear cells (PBMCs) before and during vedolizumab therapy.

Wiskott-Aldrich syndrome protein deficiency in innate immune cells leads to mucosal immune dysregulation and colitis in mice.

Background & Aims: Immunodeficiency and autoimmune sequelae, including colitis, develop in patients and mice deficient in Wiskott-Aldrich syndrome protein (WASP), a hematopoietic cell-specific intracellular signaling molecule that regulates the actin cytoskeleton. Development of colitis in WASP-deficient mice requires lymphocytes; transfer of T cells is sufficient to induce colitis in immunodeficient mice. We investigated the interactions between innate and adaptive immune cells in mucosal regulation during development of T cell-mediated colitis in mice with WASP-deficient cells of the innate immune system.

Regulatory T cells in inflammatory bowel disease.

Purpose Of Review: The intestinal immune system must orchestrate a complex balance between proinflammatory and anti-inflammatory responses to luminal antigens, and disruptions in this balance can result in inflammatory bowel disease (IBD). This review explores recent data that elucidate the role of regulatory T cells (Tregs) in the pathogenesis of IBD in mice and humans.

Recent Findings: Data from murine models of colitis implicate several novel mechanisms critical to Treg function and generation including the inhibitory cytokine interleukin-35, pericellular adenosine generation and cytokine deprivation-induced apoptosis.

Distinct roles of CTLA-4 and TGF-beta in CD4+CD25+ regulatory T cell function.

Both CTLA-4 and TGF-beta have been implicated in suppression by CD4+CD25+ regulatory T cells (Treg). In this study, the relationship between CTLA-4 and TGF-beta in Treg function was examined. Blocking CTLA-4 on wild-type Treg abrogated their suppressive activity in vitro, whereas neutralizing TGF-beta had no effect, supporting a TGF-beta-independent role for CTLA-4 in Treg-mediated suppression in vitro.

The role of CD28 and CTLA4 in the function and homeostasis of CD4+CD25+ regulatory T cells.

CD4+CD25+ T cells regulate a variety of autoimmune and alloimmune responses including the development of autoimmune diabetes in non-obese diabetic (NOD) mice. We have examined the role of CD28/CTLA4/B7 interactions in the expansion and survival of CD4+CD25+ regulatory T cells (T(reg)) in this setting. CD28/ B7 interactions are essential in the development of T(reg) in the thymus and for their survival in the periphery.

Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells.

CD28/B7 blockade leads to exacerbated autoimmune disease in the nonobese diabetic mouse strain as a result of a marked reduction in the number of CD4(+)CD25(+) regulatory T cells (Tregs). Herein, we demonstrate that CD28 controls both thymic development and peripheral homeostasis of Tregs. CD28 maintains a stable pool of peripheral Tregs by both supporting their survival and promoting their self-renewal.