Using Participatory Narrative Inquiry to Assess Experiences and Self-Experimentation with Diet Interventions in Inflammatory Bowel Disease Patients.

Background And Aims: To improve quality of life (QoL), patients with inflammatory bowel diseases (Crohn's disease and ulcerative colitis) often self-experiment with lifestyle changes such as dietary modifications. The nature (e.g.

DAMP-ing IBD: Extinguish the Fire and Prevent Smoldering.

In inflammatory bowel diseases (IBD), the most promising therapies targeting cytokines or immune cell trafficking demonstrate around 40% efficacy. As IBD is a multifactorial inflammation of the intestinal tract, a single-target approach is unlikely to solve this problem, necessitating an alternative strategy that addresses its variability. One approach often overlooked by the pharmaceutically driven therapeutic options is to address the impact of environmental factors.

A multiscale hybrid model for exploring the effect of Resolvin D1 on macrophage polarization during acute inflammation.

Dysregulated inflammation underlies various diseases. Specialized pro-resolving mediators (SPMs) like Resolvin D1 (RvD1) have been shown to resolve inflammation and halt disease progression. Macrophages, key immune cells that drive inflammation, respond to the presence of RvD1 by polarizing to an anti-inflammatory type (M).

Modulation of macrophage inflammatory function through selective inhibition of the epigenetic reader protein SP140.

Background: SP140 is a bromodomain-containing protein expressed predominantly in immune cells. Genetic polymorphisms and epigenetic modifications in the SP140 locus have been linked to Crohn's disease (CD), suggesting a role in inflammation.

Results: We report the development of the first small molecule SP140 inhibitor (GSK761) and utilize this to elucidate SP140 function in macrophages.

Ambiguity about Splicing Factor 3b Subunit 3 (SF3B3) and Sin3A Associated Protein 130 (SAP130).

In 2020, three articles were published on a protein that can activate the immune system by binding to macrophage-inducible C-type lectin receptor (Mincle). In the articles, the protein was referred to as 'SAP130, a subunit of the histone deacetylase complex.' However, the Mincle ligand the authors aimed to investigate is splicing factor 3b subunit 3 (SF3B3).

Recursive ensemble feature selection provides a robust mRNA expression signature for myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disorder characterized by disabling fatigue. Several studies have sought to identify diagnostic biomarkers, with varying results. Here, we innovate this process by combining both mRNA expression and DNA methylation data.

Exclusive enteral nutrition mediates gut microbial and metabolic changes that are associated with remission in children with Crohn's disease.

A nutritional intervention, exclusive enteral nutrition (EEN) can induce remission in patients with pediatric Crohn's disease (CD). We characterized changes in the fecal microbiota and metabolome to identify the mechanism of EEN. Feces of 43 children were collected prior, during and after EEN.

Severe COVID-19: NLRP3 Inflammasome Dysregulated.

SARS-CoV-2 might directly activate NLRP3 inflammasome resulting in an endogenous adjuvant activity necessary to mount a proper adaptive immune response against the virus. Heterogeneous response of COVID-19 patients could be attributed to differences in not being able to properly downregulate NLRP3 inflammasome activation. This relates to the fitness of the immune system of the individual challenged by the virus.

Whole-Genome DNA Methylation Profiling of CD14+ Monocytes Reveals Disease Status and Activity Differences in Crohn's Disease Patients.

Crohn's disease (CD) is a multifactorial incurable chronic disorder. Current medical treatment seeks to induce and maintain a state of remission. During episodes of inflammation, monocytes infiltrate the inflamed mucosa whereupon they differentiate into macrophages with a pro-inflammatory phenotype.

Anti-TNF therapy in IBD exerts its therapeutic effect through macrophage IL-10 signalling.

Objective: Macrophage interleukin (IL)-10 signalling plays a critical role in the maintenance of a regulatory phenotype that prevents the development of IBD. We have previously found that anti-tumour necrosis factor (TNF) monoclonal antibodies act through Fcγ-receptor (FcγR) signalling to promote repolarisation of proinflammatory intestinal macrophages to a CD206+ regulatory phenotype. The role of IL-10 in anti-TNF-induced macrophage repolarisation has not been examined.

Activation of Resolution Pathways to Prevent and Fight Chronic Inflammation: Lessons From Asthma and Inflammatory Bowel Disease.

Formerly considered as a passive process, the resolution of acute inflammation is now recognized as an active host response, with a cascade of coordinated cellular and molecular events that promotes termination of the inflammatory response and initiates tissue repair and healing. In a state of immune fitness, the resolution of inflammation is contained in time and space enabling the restoration of tissue homeostasis. There is increasing evidence that poor and/or inappropriate resolution of inflammation participates in the pathogenesis of chronic inflammatory diseases, extending in time the actions of pro-inflammatory mechanisms, and responsible in the long run for excessive tissue damage and pathology.

A distinct epigenetic profile distinguishes stenotic from non-inflamed fibroblasts in the ileal mucosa of Crohn's disease patients.

Background: The chronic remitting and relapsing intestinal inflammation characteristic of Crohn's disease frequently leads to fibrosis and subsequent stenosis of the inflamed region. Approximately a third of all Crohn's disease patients require resection at some stage in their disease course. As the pathogenesis of Crohn's disease associated fibrosis is largely unknown, a strong necessity exists to better understand the pathophysiology thereof.

TNF-anti-TNF Immune Complexes Inhibit IL-12/IL-23 Secretion by Inflammatory Macrophages via an Fc-dependent Mechanism.

Background And Aims: We have recently shown that the mode of action of IgG1 anti-tumour necrosis factor [TNF] antibodies in inflammatory bowel disease [IBD] requires Fcγ-receptor [FcγR] engagement on macrophages. Here we examine the effect of Fcγ-receptor signalling by anti-TNF on macrophage IL-12/IL-23 secretion.

Methods: Cytokine production by human inflammatory macrophages was assessed at the level of RNA and protein.

Fibrostenotic Phenotype of Myofibroblasts in Crohn's Disease is Dependent on Tissue Stiffness and Reversed by LOX Inhibition.

Background And Aims: Crohn's disease is a chronic inflammatory disorder of the intestine and often leads to fibrosis, characterized by excess extracellular matrix [ECM] deposition, increased tissue stiffness, and stricture formation. Here we evaluated the contribution of myofibroblast-ECM interactions to the development of intestinal fibrosis in Crohn's disease.

Methods: Matched primary human myofibroblasts were isolated from stenotic, inflamed and normal-appearing small intestine within the same Crohn's disease patient [n = 10].

Development of Reliable, Valid and Responsive Scoring Systems for Endoscopy and Histology in Animal Models for Inflammatory Bowel Disease.

Background And Aims: Although several endoscopic and histopathologic indices are available for evaluating the severity of inflammation in mouse models of colitis, the reliability of these scoring instruments is unknown. Our aim was to evaluate the reliability of the individual items in the existing indices and develop new scoring systems by selection of the most reliable index items.

Methods: Two observers scored the histological slides [n = 224] and endoscopy videos [n = 201] from treated and untreated Interleukin[IL]-10 knock-out and T-cell transferred SCID mice.

Inhibition of miR-142-5P ameliorates disease in mouse models of experimental colitis.

Background: MicroRNAs (miRNAs) are epigenetically involved in regulating gene expression. They may be of importance in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to determine the role of miRNAs by their specific blocking in the CD4+CB45RBhi T-cell transfer model of chronic experimental colitis.

Embracing Complexity beyond Systems Medicine: A New Approach to Chronic Immune Disorders.

In order to combat chronic immune disorders (CIDs), it is an absolute necessity to understand the bigger picture, one that goes beyond insights at a one-disease, molecular, cellular, and static level. To unravel this bigger picture we advocate an integral, cross-disciplinary approach capable of embracing the complexity of the field. This paper discusses the current knowledge on common pathways in CIDs including general psychosocial and lifestyle factors associated with immune functioning.

Vagal innervation is required for the formation of tertiary lymphoid tissue in colitis.

Tertiary lymphoid tissue (TLT) is lymphoid tissue that forms in adult life as a result of chronic inflammation in a tissue or organ. TLT has been shown to form in a variety of chronic inflammatory diseases, though it is not clear if and how TLT develops in the inflamed colon during inflammatory bowel disease. Here, we show that TLT develops as newly formed lymphoid tissue in the colon following dextran sulphate sodium induced colitis in C57BL/6 mice, where it can be distinguished from the preexisting colonic patches and solitary intestinal lymphoid tissue.

Peripheral blood methylation profiling of female Crohn's disease patients.

Background: Crohn's disease (CD) is a chronic inflammatory disorder belonging to the inflammatory bowel diseases (IBD). CD affects distinct parts of the gastrointestinal tract, leading to symptoms including diarrhea, fever, abdominal pain, weight loss, and anemia. The aim of this study was to assess whether the DNA methylome of peripheral blood cells can be associated with CD in women.

Actual Usage and Quality of Experimental Colitis Models in Preclinical Efficacy Testing: A Scoping Review.

Background: There is no standardized validated experimental model used to predict human drug response, and the choice of model is not based on systematic evidence. Therefore, we decided to systematically investigate which models are currently used by selecting studies from literature that use prescribed inflammatory bowel disease medication as a positive control.

Methods: A search of PubMed was performed using terms describing experimental colitis models and the drugs used in corresponding clinical practice followed by the application of an animal filter.

Treg subsets in inflammatory bowel disease and colorectal carcinoma: Characteristics, role, and therapeutic targets.

T regulatory cells (Tregs) play an important role in the regulation of autoimmunity, autoinflammation, allergic diseases, infection, and the tumor environment. Different subsets are characterized that use a number of regulatory mechanisms. Tregs can influence the progression of inflammatory bowel disease and the development of colorectal cancer.

Elevated interleukin-8 in bile of patients with primary sclerosing cholangitis.

Background & Aims: To better understand the pathogenesis of primary sclerosing cholangitis, anti- and pro-inflammatory factors were studied in bile.

Methods: Ductal bile of PSC patients (n = 36) and controls (n = 20) was collected by endoscopic retrograde cholangiography. Gallbladder bile was collected at liver transplantation.

Similar Short- and Long-term Colectomy Rates with Ciclosporin and Infliximab Treatment in Hospitalised Ulcerative Colitis Patients.

Background And Aims: Ciclosporin A [CsA] and infliximab [IFX] are similarly effective in preventing short-term colectomy in ulcerative colitis [UC] patients, but long-term data are scarce. We aimed to compare short- and long-term efficacy of CsA and IFX by analysing colectomy rates and failure of remission-induction treatment as outcome parameters for treatment success.

Methods: We retrospectively studied hospitalised UC patients who received CsA or IFX for moderate-to-severe UC, between January 2000 and April 2014.