Epigenetic control of commensal induced Th2 Responses and Intestinal immunopathology.

Unlabelled: Understanding the initiation of T-helper (Th)-2 immunity is crucial for addressing allergic diseases that have been linked to the commensal microbiota. However, Th2 responses are notably absent from known host-microbiota intestinal immune circuits. Notably, the commensal protist induces a transient innate ILC2 circuit rather than a chronic Th2 circuit.

Eomes expression identifies the early bone marrow precursor to classical NK cells.

Natural killer (NK) cells traffic through the blood and mount cytolytic and interferon-γ (IFNγ)-focused responses to intracellular pathogens and tumors. Type 1 innate lymphoid cells (ILC1s) also produce type 1 cytokines but reside in tissues and are not cytotoxic. Whether these differences reflect discrete lineages or distinct states of a common cell type is not understood.

New Insights on Genes, Gluten, and Immunopathogenesis of Celiac Disease.

Celiac disease (CeD) is a gluten-induced enteropathy that develops in genetically susceptible individuals upon consumption of cereal gluten proteins. It is a unique and complex immune disorder to study as the driving antigen is known and the tissue targeted by the immune reaction can be interrogated. This review integrates findings gained from genetic, biochemical, and immunologic studies, which together have revealed mechanisms of gluten peptide modification and HLA binding, thereby enabling a maladapted anti-gluten immune response.

Culturally Adapted Dental Visual Aids Effect on Behavior Management during Dental Visits in Children with Autism Spectrum Disorder.

Aim: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by unique behavioral patterns, treating children with ASD in the dental clinic has been a great challenge due to their behavior. This study aims to determine the effectiveness of culturally adapted dental visual aids in modifying behavior patterns during dental visits in children with ASD.

Materials And Methods: A controlled, blinded, randomized, clinical trial, with 64 children diagnosed with ASD, were randomly divided into two groups.

Comprehensive Association Analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease.

Background & Aims: Patients with inflammatory bowel disease (IBD) frequently develop extraintestinal manifestations (EIMs) that contribute substantially to morbidity. We assembled the largest multicohort data set to date to investigate the clinical, serologic, and genetic factors associated with EIM complications in IBD.

Methods: Data were available in 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs (eg, ankylosing spondylitis [ankylosing spondylitis and sacroiliitis], primary sclerosing cholangitis [PSC], peripheral arthritis, and skin and ocular manifestations) across 4 cohorts (Cedars-Sinai Medical Center, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort).

Restoring tolerance with antigen delivery.

Strategies that modulate antigen delivery are being tested to reverse autoimmunity.

Epithelial IFNγ signalling and compartmentalized antigen presentation orchestrate gut immunity.

All nucleated cells express major histocompatibility complex I and interferon-γ (IFNγ) receptor, but an epithelial cell-specific function of IFNγ signalling or antigen presentation by means of major histocompatibility complex I has not been explored. We show here that on sensing IFNγ, colonic epithelial cells productively present pathogen and self-derived antigens to cognate intra-epithelial T cells, which are critically located at the epithelial barrier. Antigen presentation by the epithelial cells confers extracellular ATPase expression in cognate intra-epithelial T cells, which limits the accumulation of extracellular adenosine triphosphate and consequent activation of the NLRP3 inflammasome in tissue macrophages.

Microbial-enrichment method enables high-throughput metagenomic characterization from host-rich samples.

Host-microbe interactions have been linked to health and disease states through the use of microbial taxonomic profiling, mostly via 16S ribosomal RNA gene sequencing. However, many mechanistic insights remain elusive, in part because studying the genomes of microbes associated with mammalian tissue is difficult due to the high ratio of host to microbial DNA in such samples. Here we describe a microbial-enrichment method (MEM), which we demonstrate on a wide range of sample types, including saliva, stool, intestinal scrapings, and intestinal mucosal biopsies.

Healthcare Experience of Pediatric Patients with Autism Spectrum Disorders in Saudi Arabia: A Cross-Sectional Study.

Children with autism spectrum disorder (ASD) face several challenges in the healthcare setting. This study defines the challenges experienced by children with autism in hospitals in Saudi Arabia. A cross-sectional study was conducted using a questionnaire for guardians of autistic children in outpatient clinics, autism support groups, and rehabilitation centers.

The gut protist Tritrichomonas arnold restrains virus-mediated loss of oral tolerance by modulating dietary antigen-presenting dendritic cells.

Loss of oral tolerance (LOT) to gluten, driven by dendritic cell (DC) priming of gluten-specific T helper 1 (Th1) cell immune responses, is a hallmark of celiac disease (CeD) and can be triggered by enteric viral infections. Whether certain commensals can moderate virus-mediated LOT remains elusive. Here, using a mouse model of virus-mediated LOT, we discovered that the gut-colonizing protist Tritrichomonas (T.

Effect of Culturally Adapted Dental Visual Aids on Anxiety Levels in Children with Autism Spectrum Disorder: A Randomized Clinical Trial.

Autism spectrum disorder (ASD) prevalence has risen dramatically in recent decades; it is now common for children with ASD to seek dental care. Because their distinct behavioral patterns prevent them from receiving dental care in a traditional dental clinic, structured dental visual aids are required to help prepare them for their dental appointment. This study aimed to test the effect of "culturally adapted dental visual aids" in decreasing anxiety levels during dental visits in children with autism spectrum disorder (ASD).

Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is an immune-mediated disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single-cell transcriptomics, and T and B cell receptor repertoire analysis of right colon tissue from 65 patients with PSC, 108 patients with IBD and 48 healthy individuals we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia in patients with PSC.

Microbes with higher metabolic independence are enriched in human gut microbiomes under stress.

A wide variety of human diseases are associated with loss of microbial diversity in the human gut, inspiring a great interest in the diagnostic or therapeutic potential of the microbiota. However, the ecological forces that drive diversity reduction in disease states remain unclear, rendering it difficult to ascertain the role of the microbiota in disease emergence or severity. One hypothesis to explain this phenomenon is that microbial diversity is diminished as disease states select for microbial populations that are more fit to survive environmental stress caused by inflammation or other host factors.

Parental Knowledge and Awareness about Shaken Baby Syndrome in Jeddah, Saudi Arabia: A Cross-Sectional Study.

Background: Despite the serious consequences of shaken baby syndrome (SBS), previous studies revealed a low level of knowledge among Saudi parents.

Methods: This is a cross-sectional study. An electronic questionnaire was distributed through social media platforms to parents of pediatric age group children in Jeddah, Saudi Arabia.

Genetic coding variant in complement factor B (CFB) is associated with increased risk for perianal Crohn's disease and leads to impaired CFB cleavage and phagocytosis.

Objective: Perianal Crohn's disease (pCD) occurs in up to 40% of patients with CD and is associated with poor quality of life, limited treatment responses and poorly understood aetiology. We performed a genetic association study comparing CD subjects with and without perianal disease and subsequently performed functional follow-up studies for a pCD associated SNP in ().

Design: Immunochip-based meta-analysis on 4056 pCD and 11 088 patients with CD from three independent cohorts was performed.

Metabolic independence drives gut microbial colonization and resilience in health and disease.

Background: Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge.

Results: Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments.

Prenatal maternal stress and the severity of autism spectrum disorder: A cross-sectional study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder linked to several genetic and environmental factors including antenatal stress. Hence, we aimed to examine whether a mother's stress during pregnancy is associated with the severity of autism spectrum disorder in children. The study was conducted with 459 mothers of children with autism (aged 2-14 years) who were attending rehabilitation and educational centers in the two major cities of Makkah and Jeddah in Saudi Arabia.

GATA4 controls regionalization of tissue immunity and commensal-driven immunopathology.

There is growing recognition that regionalization of bacterial colonization and immunity along the intestinal tract has an important role in health and disease. Yet, the mechanisms underlying intestinal regionalization and its dysregulation in disease are not well understood. This study found that regional epithelial expression of the transcription factor GATA4 controls bacterial colonization and inflammatory tissue immunity in the proximal small intestine by regulating retinol metabolism and luminal IgA.

LRP-1 links post-translational modifications to efficient presentation of celiac disease-specific T cell antigens.

Celiac disease (CeD) is an autoimmune disorder in which gluten-derived antigens trigger inflammation. Antigenic peptides must undergo site-specific deamidation to be presentable to CD4 T cells in an HLA-DQ2 or -DQ8 restricted manner. While the biochemical basis for this post-translational modification is understood, its localization in the patient's intestine remains unknown.

Paired bone marrow and peripheral blood samples demonstrate lack of widespread dissemination of some CH clones.

Clonal hematopoiesis (CH) represents clonal expansion of mutated hematopoietic stem cells detectable in the peripheral blood or bone marrow through next generation sequencing. The current prevailing model posits that CH mutations detected in the peripheral blood mirror bone marrow mutations with clones widely disseminated across hematopoietic compartments. We sought to test the hypothesis that all clones are disseminated throughout hematopoietic tissues by comparing CH in hip vs peripheral blood specimens collected at the time of hip replacement surgery.

Maladaptive consequences of inflammatory events shape individual immune identity.

The vertebrate immune system develops in layers, as modes of immunity have evolved on top of each other through time with the expansion of organismal complexity. The maturation timing of immune cell subsets, such as innate immune cells, innate-like cells and adaptive cells, corresponds to their physiological roles in protective immunity. While various cell subsets have specialized roles, they also complement each other to clear pathogens, resolve inflammation and maintain homeostasis, especially at barrier sites with high microbial density.