Integrated Analysis Of Biopsies From Inflammatory Bowel Disease Patients Identifies SAA1 As A Link Between Mucosal Microbes With TH17 And TH22 Cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE97012 | GEO | 2017/11/12
SECONDARY ACCESSION(S): PRJNA380408
REPOSITORIES: GEO
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Project description:BACKGROUND:Inflammatory bowel diseases (IBD) are believed to be driven by dysregulated interactions between the host and the gut microbiota. Our goal is to characterize and infer relationships between mucosal T cells, the host tissue environment, and microbial communities in patients with IBD who will serve as basis for mechanistic studies on human IBD. METHODS:We characterized mucosal CD4 T cells using flow cytometry, along with matching mucosal global gene expression and microbial communities data from 35 pinch biopsy samples from patients with IBD. We analyzed these data sets using an integrated framework to identify predictors of inflammatory states and then reproduced some of the putative relationships formed among these predictors by analyzing data from the pediatric RISK cohort. RESULTS:We identified 26 predictors from our combined data set that were effective in distinguishing between regions of the intestine undergoing active inflammation and regions that were normal. Network analysis on these 26 predictors revealed SAA1 as the most connected node linking the abundance of the genus Bacteroides with the production of IL17 and IL22 by CD4 T cells. These SAA1-linked microbial and transcriptome interactions were further reproduced with data from the pediatric IBD RISK cohort. CONCLUSIONS:This study identifies expression of SAA1 as an important link between mucosal T cells, microbial communities, and their tissue environment in patients with IBD. A combination of T cell effector function data, gene expression and microbial profiling can distinguish between intestinal inflammatory states in IBD regardless of disease types.
| S-EPMC5613756 | biostudies-literature
Project description:Inflammatory bowel diseases (IBD) are believed to be driven by dysregulated interactions between the host and the gut microbiota. Our goal is to characterize the relationships between mucosal T cells, the host tissue environment and microbial communities in IBD patients to identify new therapeutic targets. We identified 26 predictors from our combined data set that were effective in distinguishing between regions of the intestine undergoing active inflammation and regions that were normal. Network analysis on these 26 predictors revealed SAA1 as the most connected node linking the abundance of the genus Bacteroides with the production of IL17 and IL22 by CD4+ T cells. The SAA1-linked microbial and transcriptome interactions were further validated with data from the pediatric IBD RISK cohort. This study identifies expression of SAA1 as an important link between mucosal T cells, microbial communities and their tissue environment in IBD patients. A combination of FACS, gene expression and microbial profiling can distinguish between intestinal inflammatory states in IBD regardless of disease types.
2017-11-11 | GSE96665 | GEO
Project description:Integrated Analysis Of Biopsies From Inflammatory Bowel Disease Patients Identifies SAA1 As A Link Between Mucosal Microbes With TH17 And TH22 Cells
| PRJNA380408 | ENA
Project description:Graphical Abstract
| S-EPMC6300656 | biostudies-other
Project description:BACKGROUND: Immunological and genetic findings implicate Th17 effector cytokines in the pathogenesis of inflammatory bowel disease (IBD). Expression of Th17 pathway-associated genes is mainly studied in colonic disease. The present study assessed the mRNA expression levels of Th17 effector cytokines (IL17A, IL17F, IL21, IL22 and IL26) and genes involved in differentiation (IL6, IL1B, TGFB1, IL23A and STAT3) and recruitment of Th17 cells (CCR6 and CCL20) by quantitative real-time PCR analysis of colonic and ileal biopsies from 22 healthy control subjects, 26 patients with Crohn's disease (CD) and 12 patients with ulcerative colitis (UC). Inflammation was quantified by measuring expression of the inflammatory mediators IL8 and TNF. RESULTS: Evaluation of mRNA expression levels in colonic and ileal control samples revealed that TNF, TGFB1, STAT3 and CCR6 were expressed at higher levels in the ileum than in the colon. Expression of all the Th17 pathway-associated genes was increased in inflamed colonic samples. The increased expression of these genes was predominantly observed in samples from UC patients and was associated with more intense inflammation. Although increased expression of IL17A, IL17F, IL21 and IL26 was detected in inflamed ileal samples, expression of the indispensable Th17 cell differentiation factors TGFB1 and IL23A, the signaling molecule STAT3 and the Th17 recruitment factors CCR6 and CCL20 were unchanged. CONCLUSIONS: Our findings suggest that immune regulation is different in colonic and ileal disease, which might have important consequences for therapeutic intervention.
| S-EPMC3016394 | biostudies-literature
Project description:IntroductionAquaporin (AQP) channels are involved in regulating fluid homeostasis in the colon. Several AQP channels were detected in human colon epithelial cells. In a previous study, rats fed 1% (wt/wt) sodium cholate had increased AQP3, 7, and 8 levels, suggesting AQP involvement in bile acid diarrhea (BAD). Our aim was to compare AQP expressions in rectosigmoid mucosal (RSM) biopsies from patients with irritable bowel syndrome-diarrhea (IBS-D) (divided into those with normal or high fecal BA excretion) and in patients with IBS-constipation (IBS-C) compared with healthy controls.MethodsIn RSM biopsies from 44 patients with IBS-D (with normal (<) or high (>2,337 μmol/48 hours (BAD)) fecal BA excretion), 10 patients with IBS-C, and 17 healthy controls, we measured expressions of AQP1, 3, 7, and 8, with RT-PCR (housekeeper gene GAPDH). We analyzed RNA for expression by RT-PCR assays, with expression calculated using 2-based fold-change. Comparisons of IBS groups were corrected for false detection rate (Bonferroni correction for 12 comparisons; P < 0.0042). AQP protein measurements on biopsies from 3 healthy controls, 3 patients with IBS-D, and 3 patients with BAD were performed by western blots (GAPDH housekeeping protein).ResultsIn RSM from patients with IBS-D (but not IBS-C), mRNA expression of AQP3 was decreased, and AQP7 and 8 were increased relative to controls. Fold differences were not different in IBS-D with or without BAD. Western blots confirmed increased expression of AQP7 and 8 and decreased AQP3 proteins in biopsies from patients with IBS-D compared with controls.ConclusionsIncreased AQP7 and 8 and decreased AQP3 expressions in RSM suggest that further studies on AQPs' potential role in the pathophysiology of diarrhea in IBS-D are warranted.
| S-EPMC6602785 | biostudies-literature
Project description:Campylobacter concisus is an emerging pathogen associated with inflammatory bowel disease (IBD), yet little is known about the genetic diversity of C. concisus in relation to host niches and disease. We isolated 104 C. concisus isolates from saliva, mucosal biopsies and faecal samples from 41 individuals (26 IBD, 3 Gastroenteritis (GE), 12 Healthy controls (HC)). Whole genomes were sequenced and the dataset pan-genome examined, and genomic information was used for typing using multi-locus-sequence typing (MLST). C. concisus isolates clustered into two main groups/genomospecies (GS) with 71 distinct sequence types (STs) represented. Sampling site (p < 0.001), rather than disease phenotype (p = 1.00) was associated with particular GS. We identified 97 candidate genes associated with increase or decrease in prevalence during the anatomical descent from the oral cavity to mucosal biopsies to faeces. Genes related to cell wall/membrane biogenesis were more common in oral isolates, whereas genes involved in cell transport, metabolism and secretory pathways were more prevalent in enteric isolates. Furthermore, there was no correlation between individual genetic diversity and clinical phenotype. This study confirms the genetic heterogeneity of C. concisus and provides evidence that genomic variation is related to the source of isolation, but not clinical phenotype.
| S-EPMC5790007 | biostudies-literature
Project description:Inflammatory bowel disease affects more than 2 million people in Europe, with almost 20% of patients being diagnosed in pediatric age. Patients with inflammatory bowel disease are at increased risk of thromboembolic complications which may affect patients' morbidity and mortality. The risk of the most common thromboembolic events, such as deep venous thrombosis and pulmonary embolism, are estimated to be three-fold increased compared to controls, but many other districts can be affected. Moreover, patients with ulcerative colitis and Crohn's disease experience thromboembolic events at a younger age compared to general population. Many factors have been investigated as determinants of the pro-thrombotic tendency such as acquired risk factors or genetic and immune abnormalities, but a unique cause has not been found. Many efforts have been focused on the study of abnormalities in the coagulation cascade, its natural inhibitors and the fibrinolytic system components and both quantitative and qualitative alterations have been demonstrated. Recently the role of platelets and microvascular endothelium has been reviewed, as the possible link between the inflammatory and hemostatic process.
| S-EPMC4393581 | biostudies-other
Project description:Th17, Th22, and Th1 cells are detected in psoriatic skin lesions and implicated in psoriasis pathogenesis, but inflammatory T cell numbers in blood, as well as the relative importance of each cell type, is unclear. Using 7-color flow cytometry, circulating Th17, Th22, and Th1 cells were quantified in 21 untreated psoriatics and 17 healthy individuals. CCR6 was the best cell surface marker for IL-17A+ cells when compared with IL-23R or CD161. CCR6+, IL-17A+, IL-22+, CCR6+IL-17A+, CCR6+IL-22+, CCR6+tumor necrosis factor-alpha+, IL-17A+IFN-gamma-, IL-17A+IL-22+IFN-gamma-, and IL-17A+IL-22-IFN-gamma- cells were increased in psoriatics (all values P<0.001), indicating elevations in circulating Th17 cells, using multiple criteria to define these cells. Th22 (IL-17A-IL-22+IFN-gamma-, P<0.05) and Th1 (IL-17A-IFN-gamma+, P<0.05) cells were also increased in psoriatics, but to a lesser extent. Inhibition of either NF-kappaB or STAT3 in vitro blocked cytokine production by both Th17 and Th1 cells. Circulating levels of Th17 and Th1 cells decreased in a subset of five psoriasis patients serially evaluated following induction therapy with infliximab. In summary, elevated numbers of circulating inflammatory T cells may contribute to cutaneous inflammation and systemic inflammatory disease that occurs in individuals with psoriasis.
| S-EPMC2892169 | biostudies-literature
Project description:BackgroundRecently, increased interleukin (IL)-24 expression has been demonstrated in the colon biopsies of adult patients with inflammatory bowel disease (IBD). However, the role of IL-24 in the pathomechanism of IBD is still largely unknown.MethodsPresence of IL-24 was determined in the samples of children with IBD and in the colon of dextran sodium sulfate (DSS) treated mice. Effect of inflammatory factors on IL24 expression was determined in peripheral blood (PBMCs) and lamina propria mononuclear cells (LPMCs). Also, the impact of IL-24 was investigated on HT-29 epithelial cells and CCD-18Co colon fibroblasts. Expression of tissue remodeling related genes was investigated in the colon of wild type (WT) mice locally treated with IL-24 and in the colon of DSS treated WT and Il20rb knock out (KO) mice.ResultsIncreased amount of IL-24 was demonstrated in the serum and colon samples of children with IBD and DSS treated mice compared to that of controls. IL-1β, LPS or H2O2 treatment increased the expression of IL24 in PBMCs and LPMCs. IL-24 treatment resulted in increased amount of TGF-β and PDGF-B in HT-29 cells and enhanced the expression of extracellular matrix (ECM)-related genes and the motility of CCD-18Co cells. Similarly, local IL-24 treatment increased the colonic Tgfb1 and Pdgfb expression of WT mice. Moreover, expression of pro-fibrotic Tgfb1 and Pdgfb were lower in the colon of DSS treated Il20rb KO compared to that of WT mice. The disease activity index of colitis was less severe in DSS treated Il20rb KO compared to WT mice.ConclusionOur study suggest that IL-24 may play a significant role in the mucosal remodeling of patients with IBD by promoting pro-fibrotic processes.
| S-EPMC8173892 | biostudies-literature