scholarly journals Crohn’s Disease Patients in Remission Display an Enhanced Intestinal IgM+ B Cell Count in Concert with a Strong Activation of the Intestinal Complement System

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 78 ◽  
Author(s):  
Sophie Preisker ◽  
Ann-Kathrin Brethack ◽  
Arne Bokemeyer ◽  
Dominik Bettenworth ◽  
Christian Sina ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Complement System ◽  
Expression Patterns ◽  
Critical Role ◽  
Mucosal Immune Response ◽  
Immunoglobulin M ◽  
Complement Components ◽  
Activation Pathways ◽  
Definition Of

Inflammatory bowel disease (IBD) is an umbrella term that comprises Crohn’s disease (CD) and ulcerative colitis (UC). Both entities are characterized by a disturbed mucosal immune response and an imbalance of intestinal microbiota composition. The complement system (C) plays a critical role in the detection, and clearance of bacteria and dysregulation of single complement components has been linked to IBD. Here, we asked if the C contributes to distinct subtypes of inflammation observed in CD and UC. We performed systematical expression analyses of the intestinal C in IBD patients and controls. Immunohistochemistry or immunoblot experiments were performed to verify qPCR data. Activity of the three activation pathways of C was studied in sera samples. In CD patients a strong upregulation of the C was observed enabling the definition of unique expression patterns being associated either with remission or active disease. These data were reflected by an enhanced C activation in sera and fecal samples. An excessive mucosal presence of immunoglobulin M (IgM) and CR2/CD21 positive B cells in concert with decreased fecal IgA level was identified in CD patients in remission. These findings point to an exacerbated induction of the intestinal C that may potentially be involved in the etiology of CD.

scholarly journals Revealing immune responses in the Mycobacterium avium subsp. paratuberculosis-infected THP-1 cells using single cell RNA-sequencing

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254194
Author(s):  
Hong-Tae Park ◽  
Woo Bin Park ◽  
Suji Kim ◽  
Jong-Sung Lim ◽  
Gyoungju Nah ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Single Cell ◽  
Mycobacterium Avium ◽  
Expression Patterns ◽  
Cell Types ◽  
Marker Genes ◽  
Specific Marker ◽  
Cell Type ◽  
Cytokines And Chemokines

Mycobacterium avium subsp. paratuberculosis (MAP) is a causative agent of Johne’s disease, which is a chronic and debilitating disease in ruminants. MAP is also considered to be a possible cause of Crohn’s disease in humans. However, few studies have focused on the interactions between MAP and human macrophages to elucidate the pathogenesis of Crohn’s disease. We sought to determine the initial responses of human THP-1 cells against MAP infection using single-cell RNA-seq analysis. Clustering analysis showed that THP-1 cells were divided into seven different clusters in response to phorbol-12-myristate-13-acetate (PMA) treatment. The characteristics of each cluster were investigated by identifying cluster-specific marker genes. From the results, we found that classically differentiated cells express CD14, CD36, and TLR2, and that this cell type showed the most active responses against MAP infection. The responses included the expression of proinflammatory cytokines and chemokines such as CCL4, CCL3, IL1B, IL8, and CCL20. In addition, the Mreg cell type, a novel cell type differentiated from THP-1 cells, was discovered. Thus, it is suggested that different cell types arise even when the same cell line is treated under the same conditions. Overall, analyzing gene expression patterns via scRNA-seq classification allows a more detailed observation of the response to infection by each cell type.

scholarly journals Regulatory T-cell therapy in Crohn’s disease: challenges and advances

Gut ◽  
2020 ◽  
Vol 69 (5) ◽  
pp. 942-952 ◽  
Author(s):  
Jennie N Clough ◽  
Omer S Omer ◽  
Scott Tasker ◽  
Graham M Lord ◽  
Peter M Irving
Keyword(s):  
T Cells ◽  
Crohn’S Disease ◽  
T Cell ◽  
Crohn's Disease ◽  
Regulatory T Cells ◽  
Cell Therapy ◽  
Regulatory T Cell ◽  
Critical Role ◽  
Significant Proportion ◽  
T Cell Therapy

The prevalence of IBD is rising in the Western world. Despite an increasing repertoire of therapeutic targets, a significant proportion of patients suffer chronic morbidity. Studies in mice and humans have highlighted the critical role of regulatory T cells in immune homeostasis, with defects in number and suppressive function of regulatory T cells seen in patients with Crohn’s disease. We review the function of regulatory T cells and the pathways by which they exert immune tolerance in the intestinal mucosa. We explore the principles and challenges of manufacturing a cell therapy, and discuss clinical trial evidence to date for their safety and efficacy in human disease, with particular focus on the development of a regulatory T-cell therapy for Crohn’s disease.

scholarly journals L’ALTRA PARTE DI NOI – IL MICROBIOMA UMANO

2013 ◽  
Author(s):  
Paolo Landini
Keyword(s):  
Crohn’S Disease ◽  
Immune System ◽  
Crohn's Disease ◽  
Beneficial Effect ◽  
Human Microbiota ◽  
Pathological Conditions ◽  
Beneficial Microorganisms ◽  
Potential Impact ◽  
Definition Of

The importance of microorganisms associated with man, the so-called “human microbiota” has become increasingly clear from recent scientific studies. Although it has been known for many years that some microorganisms might have a beneficial effect on processes such as digestion or on the immune system, the specific mechanisms of these phenomena have never been thoroughly studied. However, in recent years the prevalence of either beneficial microorganisms or harmful bacteria, even though not strictly pathogenic, has been associated with pathological conditions such as obesity, Crohn’s disease, atherosclerosis, and other diseases in which a bacterial component had never been implicated. In this report, I describe the main concepts related to the definition of microbiome and the potential impact of studying the mechanisms of man-microbiome interaction on the treatment of several illnesses.

scholarly journals P049 Lewis score: a useful tool for the diagnosis but not for the definition of prognosis in suspected Crohn's disease

2017 ◽  
Vol 11 (suppl_1) ◽  
pp. S102-S103
Author(s):  
M. Silva ◽  
H. Cardoso ◽  
A. Peixoto ◽  
M. Marques ◽  
E. Rodrigues-Pinto ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Definition Of

scholarly journals Fine and ultrafine particles of the diet: influence on the mucosal immune response and association with Crohn’s disease

2002 ◽  
Vol 61 (1) ◽  
pp. 123-130 ◽  
Author(s):  
Miranda C. E. Lomer ◽  
Richard P. H. Thompson ◽  
Jonathan J. Powell
Keyword(s):  
Crohn’S Disease ◽  
Gastrointestinal Tract ◽  
Crohn's Disease ◽  
Immune Responses ◽  
Ultrafine Particles ◽  
Activity Index ◽  
Food Additives ◽  
Disease Activity Index ◽  
Mucosal Immune Response ◽  
Double Blind

Crohn’s disease is a modern Western disease characterised by transmural inflammation of the gastrointestinal tract. It is of unknown aetiology, but evidence suggests that it results from a combination of genetic predisposition and environmental factors. Bacterial-sized microparticles (0·1–1·0 µm) are potent adjuvants in model antigen-mediated immune responses and are increasingly associated with disease. Microparticles of TiO2 and aluminosilicate accumulate in macrophages of human gut-associated lymphoid tissue where the earliest signs of lesions in Crohn’s disease are observed. Dietary microparticles are of endogenous or exogenous origin. Endogenous microparticles dominate and are calcium phosphate (most probably hydroxyapatite), which precipitates in the lumen of the mid-distal gastrointestinal tract due to secretion of Ca and phosphate in the succus entericus. Exogenous dietary microparticles are contaminants (soil and/or dust) and food additives. TiO2, for example, is a food colourant, and aluminosilicates are anti-caking agents, although some aluminosilicates occur as natural contaminants. Food additives alone account for ingestion of approximately 1012 particles/person per d. Possible mechanisms for the role of exogenous and endogenous dietary microparticles in promoting toleragenic or immune responses of gastrointestinal mucosal phagocytosis are discussed. In a double-blind randomised pilot study we have shown that a diet low in Ca and exogenous microparticles appears to alleviate the symptoms of ileal Crohn’s disease, with a significant (P = 0·002) improvement in the Crohn’s disease activity index. A multi-centre trial and further mechanistic studies at the cellular level are underway.

scholarly journals P048 Mucosal macrophages express elevated levels of HDAC9 in inflamed and uninflamed mucosa of Crohn’s disease, but not ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S157-S157
Author(s):  
M Ghiboub ◽  
J de Bruyn ◽  
K Reedquist ◽  
T Radstake ◽  
C Wichers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Histone Deacetylases ◽  
Cell Function ◽  
Mrna Level ◽  
Critical Role ◽  
Histone Deacetylation ◽  
Inflamed Tissue

Abstract Background Histone deacetylases (HDACs) are a group of enzymes that control histone and non-histone deacetylation and influence inflammatory gene transcription. Certain members of the HDAC family control the function of macrophages and play an important role in immune response. In this study, we aimed to study the expression of HDACs in mucosal macrophages isolated from inflammatory bowel diseases (IBD) patients. Methods Both macroscopically inflamed and non-inflamed colon resection tissue were collected from 15 Crohn’s disease (CD) and nine ulcerative colitis (UC) patients operated on for therapy refractory disease. Of the CD patients, 53% had ileal and 47% ileocolonic disease. Of the UC patients, 44% had left-sided colitis and 56% pancolitis. Lamina propria was separated from the muscularis externa, and a targeted array for epigenetic enzymes was performed. To assess the relevance of HDAC9 gene expression in terms of protein level, immunofluorescence staining of HDAC9 protein was undertaken in tissue sections from inflamed and non-inflamed mucosa. CD68 was used as a pan-macrophage marker. Results From our array, expression of HDAC9 was significantly higher in the inflamed mucosa of CD patients compared with UC patients (p = 0.005). Gene expression of HDAC9 in non-inflamed mucosa from CD was elevated compared with non-inflamed mucosa from UC. In addition, in CD, HDAC9 mRNA level was increased in inflamed tissue in comparison to non-inflamed tissue (p = 0.046). In conjunction with the expression data, HDAC9 protein was found highly expressed in inflamed tissue. HDAC9 was predominantly localised in the cytoplasmic compartment of macrophages in non-inflamed tissue whilst HDAC9 localised to the nucleus of macrophages in inflamed tissue. Conclusion HDAC9 is member of class IIA HDAC superfamily that exerts pro-inflammatory properties. The inhibition of HDAC9 in experimental murine colitis clearly enhances regulatory T-cell function, suggesting a critical role for HDAC9 in breaching immune homeostasis (de Zoeten EF et al, 2009). We suggest here that HDAC9 can serve as an additional marker to distinguish CD from UC in tissue biopsies. Furthermore, we show for the first time that HDAC9 protein is expressed in mucosal macrophages of CD patients, indicating its potential in mediating macrophage inflammatory function in IBD. Further studies are currently being undertaken to elucidate the role of HDAC9 in CD pathogenesis.

Innate Myeloid Cell Subset-Specific Gene Expression Patterns in the Human Colon are Altered in Crohn’s Disease Patients

Digestion ◽  
2018 ◽  
Vol 99 (3) ◽  
pp. 194-204 ◽  
Author(s):  
Yuki Sekido ◽  
Yoshiaki Yasumizu ◽  
Junichi Nishimura ◽  
Hisako Kayama ◽  
Hiroshi Matsuno ◽  
...  
Keyword(s):  
Gene Expression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Expression Patterns ◽  
Cell Subset ◽  
Myeloid Cell ◽  
Human Colon ◽  
Gene Expression Patterns ◽  
Specific Gene ◽  
Specific Gene Expression

Clinical phenotype and gene expression profile in Crohn's disease

2007 ◽  
Vol 292 (1) ◽  
pp. G298-G304 ◽  
Author(s):  
Claudio Csillag ◽  
Ole Haagen Nielsen ◽  
Rehannah Borup ◽  
Finn Cilius Nielsen ◽  
Jørgen Olsen
Keyword(s):  
Gene Expression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intracellular Transport ◽  
Clinical Phenotype ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Principal Component ◽  
Gene Profiling ◽  
Gene Expression Patterns

The clinical course varies significantly among patients with Crohn's disease (CD). This study investigated whether gene expression profiles generated by DNA microarray technology might predict disease progression. Biopsies from the descending colon were obtained colonoscopically from 40 CD patients. Gene profiling analyses were performed using a Human Genome U133 Plus 2.0 GeneChip Array, and summarization into a single expression measure for each probe set was performed using the robust multiple array procedure. Principal component analysis demonstrated that three components explain two-thirds of the total variation. The most important parameters for the determination of the colonic gene expression patterns were the presence of disease (CD) and presence of inflammation. Superimposition of clinical phenotype data revealed a grouping of the samples from patients with stenosis toward negative values on the axis of the second principal component. The functional annotation analysis suggested that the expression of genes involved in intracellular transport and cytoskeletal organization might influence the development of stenosis. In conclusion, even though most variation in the colonic gene expression patterns is due to presence or absence of CD and inflammation status, the development of stenosis is a parameter that affects colonic gene expression to some extent.

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