Similar Datasets
Project description:Adult inflammatory bowel disease is incompletely understood. We combine unbiased single-cell RNA sequencing (gene expression profiling, CITE-seq derived cell surface protein data, TCR and BCR sequence data) with unbiased spatial transcriptomics to interrogate changes across immune and non-immune populations in colitis and health, across tissue and blood. We compare idiopathic ulcerative colitis with hitherto under-studied immune checkpoint therapy induced colitis, utilizing non-inflamed disease states as additional controls. We identify patterns of inflammation and response unique and common to both diseases, and infer changes in cell trafficking with potential therapeutic implications. We go on to localize disease-specific changes in tissue using spatial transcriptomics, leveraging this data to interrogate cellular interactions in an unbiased manner, allowing us to describe novel microdomains of inflammation and repair.
2024-04-12 | GSE189184 | GEO
Project description:Adult inflammatory bowel disease is incompletely understood. We combine unbiased single-cell RNA sequencing (gene expression profiling, CITE-seq derived cell surface protein data, TCR and BCR sequence data) with unbiased spatial transcriptomics to interrogate changes across immune and non-immune populations in colitis and health, across tissue and blood. We compare idiopathic ulcerative colitis with hitherto under-studied immune checkpoint therapy induced colitis, utilizing non-inflamed disease states as additional controls. We identify patterns of inflammation and response unique and common to both diseases, and infer changes in cell trafficking with potential therapeutic implications. We go on to localize disease-specific changes in tissue using spatial transcriptomics. We leverage this data to interrogate cellular interactions in an unbiased manner, allowing us to describe novel microdomains of inflammation and repair.
2024-04-12 | GSE189040 | GEO
Project description:Adult inflammatory bowel disease is incompletely understood. We combine unbiased single-cell RNA sequencing (gene expression profiling, CITE-seq derived cell surface protein data, TCR and BCR sequence data) with unbiased spatial transcriptomics to interrogate changes across immune and non-immune populations in colitis and health, across tissue and blood. We compare idiopathic ulcerative colitis with hitherto under-studied immune checkpoint therapy induced colitis, utilizing non-inflamed disease states as additional controls. We identify patterns of inflammation and response unique and common to both diseases, and infer changes in cell trafficking with potential therapeutic implications. We go on to localize disease-specific changes in tissue using spatial transcriptomics. We leverage this data to interrogate cellular interactions in an unbiased manner, allowing us to describe novel microdomains of inflammation and repair.
2024-04-12 | GSE189754 | GEO
Project description:Adult inflammatory bowel disease is incompletely understood. We combine unbiased single-cell RNA sequencing (gene expression profiling, CITE-seq derived cell surface protein data, TCR and BCR sequence data) with unbiased spatial transcriptomics to interrogate changes across immune and non-immune populations in colitis and health, across tissue and blood. We compare idiopathic ulcerative colitis with hitherto under-studied immune checkpoint therapy induced colitis, utilizing non-inflamed disease states as additional controls. We identify patterns of inflammation and response unique and common to both diseases, and infer changes in cell trafficking with potential therapeutic implications. We go on to localize disease-specific changes in tissue using spatial transcriptomics. We leverage this data to interrogate cellular interactions in an unbiased manner, allowing us to describe novel microdomains of inflammation and repair.
2024-04-12 | GSE190564 | GEO
Project description:Ulcerative colitis (UC) is a major form of inflammatory bowel disease (IBD) worldwide. Better understanding of the pathogenesis of UC has led to the development of novel therapeutic agents that target specific mediators of the inflammatory cascade. A number of biological agents have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of UC and several more are currently in various phases of drug development. The commonly used agents include TNF? antagonists (e.g. infliximab, adalimumab, and golimumab) and anti-integrin agents (vedolizumab). These biological agents have profoundly influenced the management of UC patients, especially those with refractory disease. This paper reviews the currently available knowledge and evidence for the use of various biological agents in the treatment of UC.
| S-EPMC4423460 | biostudies-literature
Project description:Combination therapy is an emerging strategy that is under intensive preclinical investigation for the treatment of various diseases. CD98 is highly overexpressed on the surfaces of epithelial cells and macrophages in the colon tissue with ulcerative colitis (UC), which is usually associated with mucosal damage and inflammation. We previously proved that CD98 siRNA (siCD98)-induced down-regulation of CD98 in colitis tissue decreased the severity of UC to a certain extent. In an effort to further improve the therapeutic efficacy, we aim to simultaneously deliver siCD98 in combination with a potent anti-inflammatory agent, curcumin (CUR), using hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant spherical HA-siCD98/CUR-NPs are featured by a desirable particle size (?246 nm) and slightly negative zeta potential (?-14 mV). The NPs functionalized with HA are able to guide the co-delivery of drugs to the targeted cells related to UC therapy (colonic epithelial cells and macrophages). Compared to either siCD98- or CUR-based monotherapy, co-delivery of siCD98 and CUR by HA-functionalized NPs can exert combinational effects against UC by protecting the mucosal layer and alleviating inflammation both in vitro and in vivo. This study shows the promising capability of the co-delivered siCD98 and CUR for boosting the conventional monotherapy via this novel nanotherapeutic agent, which offers a structurally simple platform for orally administered delivery of drugs to target cells in UC therapy.
| S-EPMC5135446 | biostudies-literature
Project description:OBJECTIVES:Differentiating ulcerative colitis (UC) and Crohn disease (CD) can be clinically challenging, especially in children. Granulomatous inflammation has traditionally been attributed to CD. Crypt-associated giant cells and granulomas, however, have been observed in colonic biopsies of patients with UC. This phenomenon has not been described in the upper gastrointestinal (UGI) tract with UC. METHODS:Seven pediatric patients with UC with granulomatous UGI (gUGI) lesions were identified. Diagnosis of UC was based on symptoms, clinical course, laboratory results, imaging, and endoscopy. We compared the gUGI patients to a large cohort of pediatric patients with UC (n?=?149). RESULTS:All fully evaluated cases were associated with bloody diarrhea and moderate to severe pancolitis. Gastric and/or duodenal biopsies demonstrated giant cells or granulomas near gland destruction. Small bowel imaging did not reveal any involvement. The majority of cases responded to standard medical therapies, except for 2 patients (28.6%) who required total colectomy. Acute severe, refractory colitis (ie, colectomy within 1 month of presentation) was significantly more common in the gUGI group than the large pediatric UC group (28.6% vs 1.3%, Fisher exact P?=?0.01). CONCLUSIONS:This is the first report of pediatric UC-associated granulomatous inflammation in the UGI tract. We speculate that these lesions represent extracolonic manifestations of intense colonic disease. These atypical findings expand the diagnostic considerations that should be incorporated during the differentiation between UC and CD in the pediatric age group.
| S-EPMC5866164 | biostudies-literature
Project description:Ixekizumab is a selective monoclonal antibody targeting interleukin-17A, approved for the treatment of chronic plaque psoriasis. It has rarely been associated with inflammatory bowel disease (IBD) in randomized trials only. We report a unique case of severe new-onset ulcerative colitis in a young male complicated by cytomegalovirus infection who was on ixekizumab therapy for plaque psoriasis. We recommend that clinicians should exercise caution before prescribing ixekizumab as it seems to induce and exacerbate IBD.
| S-EPMC6244035 | biostudies-other
Project description:Background:CD1a-expressing CD14+ monocytes have been identified as inducers of autoreactive T cells. In this study, the link between inflammatory and metabolic signals and CD1a-expressing monocytes in vitro and in vivo was examined, and CD1a was evaluated as a potential therapeutic target for treatment of ulcerative colitis (UC). Methods:Peripheral blood mononuclear cells (PBMCs) from UC patients and non-UC donors were incubated with phosphatidylcholine (PC) for 2 and 7 days and subjected to flow cytometric analysis. Triacylglycerol (TAG) and cholesterol levels and frequencies of CD14+ CD1a+ monocytes were determined in a mouse model of UC that is based on NOD/scid IL2Rγnull mice reconstituted with PBMCs from UC patients (NSG-UC). NSG-UC mice were treated with anti-CD1a antibodies. Response to treatment was determined by clinical and histological scores, flow cytometric analysis of human leucocytes from the spleen and colon, and expression levels of TGFß1, HGF, IFNγ, and TARC. Results:Incubation of PBMCs with PC resulted in an increase of the frequency of CD1a+ CD14+ monocytes at the expense of CCR2-, CD86-, and TSLPR-expressing CD14+ monocytes. CD1a+ CD14+ monocytes induced the activation of CD4+ T cells and differentiation of Th cells. In vivo, TAG and cholesterol levels increased upon inflammation and correlated positively with CD14+ CD1a+ monocytes. NSG-UC mice benefitted from treatment with anti-CD1a antibodies, as indicated by a reduced histological score and reduced frequencies of CD1a+ CD14+ monocytes in the colon and spleen of mice. Conclusion:CD1a-expressing monocytes might act as sensors and mediators of inflammation in UC. Mice benefitted from treatment with anti-CD1a antibodies.
| S-EPMC6176881 | biostudies-other
Project description:Aberrant DNA methylation patterns have been reported in inflamed tissues and may play a role in disease. We studied DNA methylation and gene expression profiles of purified intestinal epithelial cells from ulcerative colitis patients, comparing inflamed and non-inflamed areas of the colon. We identified 577 differentially methylated sites (false discovery rate <0.2) mapping to 210 genes. From gene expression data from the same epithelial cells, we identified 62 differentially expressed genes with increased expression in the presence of inflammation at prostate cancer susceptibility genes PRAC1 and PRAC2. Four genes showed inverse correlation between methylation and gene expression; ROR1, GXYLT2, FOXA2, and, notably, RARB, a gene previously identified as a tumor suppressor in colorectal adenocarcinoma as well as breast, lung and prostate cancer. We highlight targeted and specific patterns of DNA methylation and gene expression in epithelial cells from inflamed colon, while challenging the importance of epithelial cells in the pathogenesis of chronic inflammation.
| S-EPMC5687324 | biostudies-literature