scholarly journals Crohn’s Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat

2021 ◽  
Vol 22 (8) ◽  
pp. 4292
Author(s):  
Ana Madeira ◽  
Carolina Serena ◽  
Miriam Ejarque ◽  
Elsa Maymó-Masip ◽  
Monica Millan ◽  
...  
Keyword(s):  
Immune Response ◽  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Wilms Tumor ◽  
Expression Profiles ◽  
Subcutaneous Fat ◽  
Hla Dr ◽  
Wide Range ◽  
Antigen Presenting

Our understanding of the interplay between human adipose tissue and the immune system is limited. The mesothelium, an immunologically active structure, emerged as a source of visceral adipose tissue. After investigating the mesothelial properties of human visceral and subcutaneous adipose tissue and their progenitors, we explored whether the dysfunctional obese and Crohn’s disease environments influence the mesothelial/mesenchymal properties of their adipocyte precursors, as well as their ability to mount an immune response. Using a tandem transcriptomic/proteomic approach, we evaluated the mesothelial and mesenchymal expression profiles in adipose tissue, both in subjects covering a wide range of body-mass indexes and in Crohn’s disease patients. We also isolated adipose tissue precursors (adipose-derived stem cells, ASCs) to assess their mesothelial/mesenchymal properties, as well as their antigen-presenting features. Human visceral tissue presented a mesothelial phenotype not detected in the subcutaneous fat. Only ASCs from mesenteric adipose tissue, named creeping fat, had a significantly higher expression of the hallmark mesothelial genes mesothelin (MSLN) and Wilms’ tumor suppressor gene 1 (WT1), supporting a mesothelial nature of these cells. Both lean and Crohn’s disease visceral ASCs expressed equivalent surface percentages of the antigen-presenting molecules human leucocyte antigen—DR isotype (HLA-DR) and CD86. However, lean-derived ASCs were predominantly HLA-DR dim, whereas in Crohn’s disease, the HLA-DR bright subpopulation was increased 3.2-fold. Importantly, the mesothelial-enriched Crohn’s disease precursors activated CD4+ T-lymphocytes. Our study evidences a mesothelial signature in the creeping fat of Crohn’s disease patients and its progenitor cells, the latter being able to present antigens and orchestrate an immune response.

scholarly journals Microbial Signature in Adipose Tissue of Crohn’s Disease Patients

2020 ◽  
Vol 9 (8) ◽  
pp. 2448
Author(s):  
Carolina Serena ◽  
Maribel Queipo-Ortuño ◽  
Monica Millan ◽  
Lidia Sanchez-Alcoholado ◽  
Aleidis Caro ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Pathogenic Bacteria ◽  
Sulfur Metabolism ◽  
Clinical Status ◽  
Subcutaneous Fat ◽  
Intestinal Barrier ◽  
Fecal Calprotectin ◽  
Inactive Disease

Crohn’s disease (CD) is characterized by compromised immune tolerance to the intestinal commensal microbiota, intestinal barrier inflammation, and hyperplasia of creeping fat (CF) and mesenteric adipose tissue (AT), which seems to be directly related to disease activity. Gut microbiota dysbiosis might be a determining factor in CD etiology, manifesting as a low microbial diversity and a high abundance of potentially pathogenic bacteria. We tested the hypothesis that CF is a reservoir of bacteria through 16S-rRNA sequencing of several AT depots of patients with active and inactive disease and controls. We found a microbiome signature within CF and mesenteric AT from patients, but not in subcutaneous fat. We failed to detect bacterial DNA in any fat depot of controls. Proteobacteria was the most abundant phylum in both CF and mesenteric AT, and positively correlated with fecal calprotectin/C-reactive protein. Notably, the clinical status of patients seemed to be related to the microbiome signature, as those with the inactive disease showed a reduction in the abundance of pathogenic bacteria. Predictive functional profiling revealed many metabolic pathways including lipopolysaccharide biosynthesis and sulfur metabolism overrepresented in active CD relative to that in inactive CD. Our findings demonstrate that microbiota dysbiosis associated with CD pathophysiology is reflected in AT and might contribute to disease severity.

scholarly journals Gut Mesenchymal Stromal Cells in Immunity

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Valeria Messina ◽  
Carla Buccione ◽  
Giulia Marotta ◽  
Giovanna Ziccheddu ◽  
Michele Signore ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Class Ii ◽  
Immune Modulator ◽  
Hla Dr ◽  
Class Ii Mhc ◽  
Intestinal Submucosa ◽  
Antigen Presenting

Mesenchymal stromal cells (MSCs), first found in bone marrow (BM), are the structural architects of all organs, participating in most biological functions. MSCs possess tissue-specific signatures that allow their discrimination according to their origin and location. Among their multiple functions, MSCs closely interact with immune cells, orchestrating their activity to maintain overall homeostasis. The phenotype of tissue MSCs residing in the bowel overlaps with myofibroblasts, lining the bottom walls of intestinal crypts (pericryptal) or interspersed within intestinal submucosa (intercryptal). In Crohn’s disease, intestinal MSCs are tightly stacked in a chronic inflammatory milieu, which causes their enforced expression of Class II major histocompatibility complex (MHC). The absence of Class II MHC is a hallmark for immune-modulator and tolerogenic properties of normal MSCs and, vice versa, the expression of HLA-DR is peculiar to antigen presenting cells, that is, immune-activator cells. Interferon gamma (IFNγ) is responsible for induction of Class II MHC expression on intestinal MSCs. The reversal of myofibroblasts/MSCs from an immune-modulator to an activator phenotype in Crohn’s disease results in the formation of a fibrotic tube subverting the intestinal structure. Epithelial metaplastic areas in this context can progress to dysplasia and cancer.

scholarly journals DOP84 Crohn’s disease modifies the DNA methylome of human adipose-stem cells, which is only partially re-established in remission

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S123-S125
Author(s):  
C Serena ◽  
M Millan ◽  
M Ejarque ◽  
A Saera-Vila ◽  
D Monfort-Ferré ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Association Studies ◽  
Subcutaneous Fat ◽  
Human Adipose Tissue ◽  
Phagocytic Capacity ◽  
Inflammatory Profile ◽  
The Impact

Abstract Background Crohn’s disease (CD) is characterised by the expansion of mesenteric adipose tissue, termed creeping fat (CF). We previously demonstrated that human adipose-tissue stem cells (hASCs) from CF exhibit a dysfunctional phenotype, including a pro-inflammatory profile, high phagocytic capacity and weak immunosuppressive properties. Importantly, these phenotypes persist in patients in remission, and are found in all adipose depots explored including subcutaneous fat. We hypothesised that this is a consequence of epigenetic modifications. Methods Epigenome-wide association studies using the 850k EPIC Illumina array were used to explore the impact of CD on the methylation signature of hASCs isolated from the subcutaneous fat (Figure 1). Changes in the expression of differentially methylated candidate genes were validated in hASCs of patients with active/inactive CD and healthy controls (Figure 1). Conclusion hASCs of patients with CD exhibit an alter DNA-methylation and gene expression profile. Remarkably, the expression of several genes is only partially restored in patients with inactive CD. Understanding how CD shapes the functionality of hASCs is critical for investigating the complex pathophysiology of this disease, as well as for the success of cell-based therapies.

scholarly journals Expression profiling of ileal mucosa in asthma reveals upregulation of innate immunity and genes characteristic of Paneth and goblet cells

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Jan K. Nowak ◽  
Marzena Dworacka ◽  
Nazgul Gubaj ◽  
Arystan Dossimov ◽  
Zhumabek Dossimov ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Differential Expression ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
Goblet Cells ◽  
Ileal Mucosa ◽  
Significant Differential Expression ◽  
Immune Genes ◽  
Asthma Patients

Abstract Background The expression profiles of the intestinal mucosa have not been comprehensively investigated in asthma. We aimed to explore this in the Correlated Expression and Disease Association Research (CEDAR) patient cohort. Methods Differential expression analysis of ileal, transverse colon, and rectal biopsies were supplemented by a comparison of transcriptomes from platelets and leukocytes subsets, including CD4+, CD8+, CD14+, CD15+, and CD19+ cells. Asthma patients (n = 15) and controls (n = 15) had similar age (p = 0.967), body mass index (p = 0.870), similar numbers of females (80%) and smoking rates (13.3%). Results Significant differential expression was found in the ileum alone, and not in any other cell/tissue types. More genes were found to be overexpressed (1,150) than under-expressed (380). The most overexpressed genes included Fc Fragment of IgG Binding Protein (FCGBP, logFC = 3.01, pFDR = 0.015), Mucin 2 (MUC2, logFC = 2.78, pFDR = 0.015), and Alpha 1B Defensin (DEFA1B, logFC = 2.73, pFDR = 0.024). Gene ontology implicated the immune system, including interleukins 4 and 13, as well as antimicrobial peptides in this overexpression. There was concordance of gene over- (STAT1, XBP1) and underexpression (NELF, RARA) in asthma and Crohn’s disease ileum when our results were compared to another dataset (p = 3.66 × 10–7). Conclusion Ileal mucosa in asthma exhibits a specific transcriptomic profile, which includes the overexpression of innate immune genes, mostly characteristic of Paneth and goblet cells, in addition to other changes that may resemble Crohn’s disease.

Association of HLA-DR genotypes and IL-1ra gene polymorphism with treatment failure of budesonide and disease patterns in Crohn's disease

2001 ◽  
Vol 13 (12) ◽  
pp. 1431-1437 ◽  
Author(s):  
Cornelia M. Gelbmann ◽  
Gerhard Rogler ◽  
Michael Gierend ◽  
Volker Gross ◽  
Jürgen Schölmerich ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gene Polymorphism ◽  
Treatment Failure ◽  
Disease Patterns ◽  
Hla Dr

scholarly journals Maintenance Therapy in Crohn's Disease

2000 ◽  
Vol 14 (suppl c) ◽  
pp. 23C-28C ◽  
Author(s):  
Hillary Steinhart
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Maintenance Therapy ◽  
Immunosuppressive Agents ◽  
Human Antibody ◽  
Chimeric Mouse ◽  
Wide Range ◽  
Systemic Glucocorticoids ◽  
Necrosis Factor

Symptoms of active Crohn’s disease may respond to one or more of a number of classes of drug therapies. These include systemic glucocorticoids, budesonide, sulphasalazine, mesalazine (5-aminosalicylates), immunosuppressive agents and antibiotics. More recently, a chimeric mouse-human antibody to tumour necrosis factor (infliximab) has been shown to induce clinical remission and endoscopic improvement in patients with moderately active Crohn’s disease refractory to other therapies. Despite this wide range of existing therapies and the potential of emerging biological therapies, recurrent Crohn’s disease continues to be a major impediment to the fulfilment of a normal lifestyle and optimal quality of life for patients with Crohn’s disease. Many drugs known to be effective for the treatment of active disease have been tried as maintenance therapy to prevent disease relapse or recurrence following medical or surgical therapy. The available evidence suggests that most of these drugs are not as useful in maintaining remission as they are in inducing it. Systemic glucocorticoids, budesonide, mesalazine (5-aminosalicylates), sulphasalazine and antibiotics are all associated with either marginal therapeutic gain in the setting of maintenance therapy or unacceptable long term toxicity. The immunosuppressive agents azathioprine, 6-mercaptopurine and methotrexate have been shown to have a beneficial effect in maintaining remission and may be helpful as steroid-sparing agents. Repeated infusions of antitumour necrosis factor antibody maintain the improvements observed after one or two initial infusions. The relative long term safety, efficacy and cost effectiveness of the various choices of maintenance therapy remain to be determined.

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