A5084515363- Inflammatory Bowel Disease
- Single-cell and spatial transcriptomics
- Microscopic Colitis
- IL-33, ST2, and ILC Pathways
- Gut microbiota and health
- Immune cells in cancer
- Psoriasis: Treatment and Pathogenesis
- Immune Cell Function and Interaction
- Cancer Cells and Metastasis
- Mycobacterium research and diagnosis
- Helicobacter pylori-related gastroenterology studies
- Immune responses and vaccinations
- Genetic factors in colorectal cancer
- Systemic Lupus Erythematosus Research
- Hidradenitis Suppurativa and Treatments
- Autophagy in Disease and Therapy
- Immunotherapy and Immune Responses
- Autoimmune and Inflammatory Disorders Research
- Pancreatitis Pathology and Treatment
- Diet and metabolism studies
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Escherichia coli research studies
- Gastrointestinal motility and disorders
- Liver Diseases and Immunity
Hospital Clínic de Barcelona
2014-2025
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2014-2025
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2014-2025
Fundació Clínic per a la Recerca Biomèdica
2024-2025
Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer
2024
Centro de Investigación Biomédica en Red
2021-2023
Instituto de Salud Carlos III
2021
Amsterdam UMC Location University of Amsterdam
2014
Abstract Ulcerative colitis and Crohn’s disease are chronic inflammatory intestinal diseases with perplexing heterogeneity in manifestation response to treatment. While the molecular basis for this remains uncharacterized, single-cell technologies allow us explore transcriptional states within tissues at an unprecedented resolution which could further understanding of these complex diseases. Here, we apply RNA-sequencing human inflamed intestine show that largest differences among patients...
Butyrate-producing gut bacteria are reduced in patients with active inflammatory bowel disease (IBD), supporting the hypothesis that butyrate supplementation may be beneficial this setting. Nonetheless, earlier studies suggest oxidation of IBD is altered. We propose inflammation decrease epithelial consumption.Non-IBD controls and were recruited for study. Stool samples used short-chain fatty acid bacterial butyryl CoA:acetate CoA-transferase quantification. Colonic biopsies ex vivo...
Background & Aims: Despite the negative results of blocking IL-17 in Crohn's disease (CD) patients, selective modulation Th17-dependent responses warrants further study. Inhibition retinoic acid-related orphan receptor gamma (RORɣt), master regulator Th17 signature, is currently being explored inflammatory diseases. Our aim was to determine effect a novel oral RORɣt antagonist (BI119) human CD and on an experimental model intestinal inflammation. Methods: 51 patients 11 healthy subjects were...
Abstract Background The gastrointestinal mucosa, with its rich vascularization juxtaposed to the anaerobic lumen, creates a steep physiological oxygen gradient along intestinal crypt. This gradient, together soluble stromal factors, is critical for maintaining barrier homeostasis. In inflammatory bowel disease (IBD), active inflammation disturbs stem cell niche environment and perfusion 1. However, impact of factors gradients on epithelial behaviour in health IBD remains poorly understood....
Ulcerative colitis (UC) is characterized by a chronic overproduction of proinflammatory cytokines. During an acute phase, the endoplasmic reticulum (ER) overloaded and protein folding process impaired, condition named ER stress. This state induces response (unfolded (UPR)), initiated activation IRE1/Xbp-1, PERK/eIF2α, ATF6 pathways, which has previously been linked to intestinal inflammation in experimental models. stress UPR trigger proinflammatory, autophagy, apoptosis genes, addition...
Vedolizumab is an anti-α4β7 antibody approved for the treatment of ulcerative colitis [UC]. Although it assumed that vedolizumab blocks intestinal homing lymphocytes, its effects on different cell populations are not fully stablished. In order to establish unique mechanisms action in UC patients, we compared those induced by anti-tumour necrosis factor [TNF].Patients with active [endoscopic Mayo score >1] starting [n = 33] or anti-TNF 45] and controls 22] were included. Colon biopsies [at...
Janus kinase (JAK) inhibition shows promise for treatment of patients with moderate to severe Crohn's disease. We aimed provide mechanistic insights into the JAK1-selective inhibitor upadacitinib through a transcriptomics substudy on biopsies from disease CELEST.Seventy-four consented this optional substudy. Ileal and colonic were collected during endoscopy at screening week 12 or 16. RNA isolated 226 samples was analyzed by RNAseq, additional qPCR analysis. Additional receiving anti-tumor...
Over the last decades, Adherent-Invasive Escherichia coli (AIEC) has been linked to pathogenesis of Crohn’s Disease. AIEC’s characteristics, as well its interaction with gut immune system and role in intestinal epithelial barrier dysfunction, have extensively studied. Nevertheless, currently available techniques investigate cross-talk between this pathogen cells (IECs) are based on infection immortalized cell lines. Despite their many advantages, lines cannot reproduce conditions tissues,...
Recent studies have shown the efficacy of autologous haematopoietic stem cell transplantation [HSCT] in severely refractory Crohn's disease [CD] patients. HSCT is thought to eliminate auto-reactive cells; however, no specific immune reconstitution CD patients are available.We followed a group [n = 18] receiving HSCT, with 50% them achieving endoscopic drug-free remission. To elucidate mechanisms driving efficacy, we monitored changes after blood and intestine immune-cell composition. 22]...
Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) resulting from the interaction of multiple environmental, genetic immunological factors. CD5 CD6 paralogs encoding lymphocyte co-receptors involved in fine-tuning intracellular signals delivered upon antigen-specific recognition, microbial pattern recognition cell adhesion. While expression variation is known to influence some immune-mediated disorders, their role IBD remains unclear. To this end, Cd5-...
ABSTRACT Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic inflammatory intestinal diseases that show a perplexing heterogeneity in manifestations response to treatment. The molecular basis for this remains uncharacterized. We applied single-cell RNA sequencing CosMx™ Spatial Molecular Imaging human colon found the highest diversity cellular composition myeloid compartment of UC CD patients. Besides resident macrophage subsets (M0 M2), patients showed variety activated macrophages...
Abstract Background KRT17 is an epithelial "alarmin" that contributes to the early host innate immune response insults. We previously found transcription, not detectable in healthy colon, up-regulated intestinal mucosa of patients with active ulcerative colitis (UC). Here, we aimed characterize cells expressing UC and explore contribution environment promoting emergence this cell population. Methods conducted single-cell RNAseq (scRNA-seq) on compartment biopsies from a cohort...
Abstract Background Infiltration of neutrophils is the main histological feature in active inflammatory bowel disease (IBD). Recent data suggests that tissue- and tumour-infiltrating can adopt remarkably different phenotypes with potentially functions. However, heterogeneity this population IBD remains unknown. Methods Single-cell RNA sequencing (scRNA-seq) was generated from colonic biopsies 92 individuals including 6 healthy controls (HC), 36 inactive IBD, 19 Crohn’s (CD) 31 ulcerative...
Abstract Background We previously showed that ulcerative colitis (UC) patients refractory to tofacitinib present an increase in the activation and pro-inflammatory profile of intestinal macrophages1. However, mechanism by which promotes further macrophages these group remains unknown. Methods Blood monocytes from healthy individuals were cultured presence M-CSF as described2. The differentiated treated with LPS (10ng/ml), TNF (20ng/ml) or IFNγ (5ng/ml) absence (300nM). effect on gene...
Abstract Background The ALI (air liquid-interface) culture derived from human primary intestinal epithelium is generating considerable interest for closely reproducing the mature cell features of differentiated in a 2D configuration. However, phenotypic changes occurring during differentiation have thus far not been explored depth. Here, we aimed to characterize composition over time. Methods 3D epithelial organoids (n=3) were expanded colonic samples and organoid-derived single cells seeded...
Abstract Background Tofacitinib is an oral JAK1 and JAK3 inhibitor approved for the treatment of moderate to severe ulcerative colitis (UC). The aim this study identify relevant cellular subsets genes involved in response and/or resistance tofacitinib using temporal single-cell RNA sequencing (scRNA-seq). Methods Colon biopsies from patients with active UC starting 10 mg bid 8 weeks 5 or thereafter were collected at baseline (n=11) during follow-up (week 8, 16, 24 48; n=12 samples) processed...
The intestinal epithelium is the interface between microbiota and underlying host mucosa. Intrinsic genetic as well acquired defects in have been described inflammatory bowel diseases (IBDs) including Crohn’s disease (CD). Bacterial metabolites, such short chain fatty acids (SCFAs), are known to exert homeostatic, anti-inflammatory anti-tumoural effects. However, effects of SCFAs context inflammation specifically CD, not extensively addressed. Results from our group reveal that epithelial...
Crohn’s disease (CD) is a chronic inflammatory bowel (IBD) with onset occurring from childhood to late age. Despite comparable genetic susceptibility, phenotype and natural history vary between paediatric adult-onset CD. Recent studies have highlighted the importance of intestinal epithelial barrier in pathogenesis IBD [1] [2] [3]. We hypothesise that epithelium patients CD characterised by age-dependent differences gene expression signature. Biopsy samples ileum colon adult were collected....
Vedolizumab (VDZ) was approved for IBD treatment in 2014. It targets the integrin ɑ4β7, which facilitates migration of leucocytes to intestine. VDZ achieves clinical remission <45% ulcerative colitis (UC) patients, and currently there are no predictors response guide decisions. Our aim unravel mechanism action underlying by assessing its effect UC patients how they correlate with response/remission VDZ. In this regard, our specific objectives were: (1) analyse frequencies leukocytes...
Abstract Background Janus Kinases (JAK), including JAK1, JAK2, JAK3 and TYK2, have garnered increasing interest as therapeutic targets for several chronic inflammatory diseases such bowel disease (IBD). Although oral small molecule JAK inhibitors are being used in the clinics an effective treatment moderate-to-severe ulcerative colitis, nonethelessthey can lead to severe systemic immunosuppression, which is associated with increased risk of infections. Our project aimed develop a...