scholarly journals P063 The immunological landscape of intestinal fibrosis in Crohn’s Disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S168-S169
Author(s):  
I Jacobs ◽  
B Creyns ◽  
G Dragoni ◽  
J Cremer ◽  
G Bislenghi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Immune Cells ◽  
Flow Cytometric Analysis ◽  
Rank Test ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Fibrotic Tissue ◽  
Alternatively Activated

Abstract Background Patients with Crohn’s disease (CD) often develop strictures, necessitating surgical intervention. The immune pathways expressed in the fibrotic regions, especially in the deeper intestinal layers, are poorly characterized hence hampering therapeutic development for anti-fibrotic agents. We performed a detailed analysis of the immune cell populations in both inflammation and fibrosis in the mucosa and deeper intestinal layers in CD patients. Methods Patients with stricturing CD (n=25) or colorectal cancer (CRC, n=10), undergoing ileocolonic resection were included. The resection specimen of CD patients was macroscopically subdivided into fibrotic, inflammatory but not fibrotic, and unaffected regions by an IBD-experienced histopathologist. The mucosal layer was furthermore separated from the deeper intestinal layers. Immune cells were isolated, followed by flow cytometry. Quantitative real time PCR (qRT-PCR) was performed for the eosinophil chemoattractant CCL11 coding for eotaxin-1 and normalized against the housekeeping genes RPL13a and PPIA. Wilcoxon matched-pairs sign rank test was performed on paired samples while Dunn’s multiple testing was performed for unpaired comparisons. Results Flow cytometric analysis in CD patients showed mainly B cell enrichment in fibrotic tissue compared to the unaffected tissue, both in the mucosa (30.2% vs 20.9% of CD45+ cells, p=0.001) as in deeper layers (34.4% vs 24.1% of CD45+ cells, p=0.01) (figure 1). Mature dendritic cells (mDC), alternatively-activated macrophages and eosinophils were also enriched but in the deeper layers of the fibrotic segment compared to the mucosa (4.3% vs 3.4%, 1.07% vs 0.04% and 2.3% vs 1.5% of CD45+ cells; p = 0.02, 0.008 and 0.02) (figure 2). Moreover, increased eosinophilic presence was also shown in the unaffected CD region compared to the fibrotic area, both in deeper layers (4.0% vs 2.3% of CD45+ cells; p=0.03) as the mucosa (2.4% vs 1.5% of CD45+ cells; p=0.01) as well as in the inflamed deeper layers compared to the superficial layers (3.3% vs 2.1% of CD45+ cells, p=0.04). These data were corroborated by increased CCL11 mRNA expression, in the deeper layers of fibrotic tissue compared to the mucosa (52.3% vs 31.0%, p=0.03). Conclusion Our results suggest a role for innate immune cells in CD complicated with fibrosis. Especially in the deeper layers, eosinophils, mature dendritic cells and alternatively-activated macrophages are implicated. The eosinophilic enrichment in the deeper layers may partly be attributed to an increased eosinophil recruitment by CCL11. Our results offer opportunities for anti-fibrotic drug development in CD.

scholarly journals Defective macrophage function in crohn's disease: role of alternatively activated macrophages in inflammation

Gut ◽  
2011 ◽  
Vol 60 (Suppl 1) ◽  
pp. A143-A144 ◽  
Author(s):  
C. Karaiskos ◽  
B. N. Hudspith ◽  
T. Elliott ◽  
N. B. Rayment ◽  
V. Avgousti ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Macrophage Function ◽  
Alternatively Activated

scholarly journals Defective Macrophage Function in Crohn's Disease: Role of Alternatively Activated Macrophages in Inflammation

2011 ◽  
Vol 140 (5) ◽  
pp. S-324-S-325
Author(s):  
Christos Karaiskos ◽  
Barry N. Hudspith ◽  
Tim Elliott ◽  
Neil B. Rayment ◽  
Vanessa Avgousti ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Macrophage Function ◽  
Alternatively Activated

scholarly journals A phased strategy to differentiate human CD14+monocytes into classically and alternatively activated macrophages and dendritic cells

BioTechniques ◽  
2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Jelani C. Zarif ◽  
James R. Hernandez ◽  
James E. Verdone ◽  
Scott P. Campbell ◽  
Charles G. Drake ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Alternatively Activated

Successful classification of macrophage-mannose receptor CD206 in severity of anti-MDA5 antibody positive dermatomyositis associated ILD

Rheumatology ◽  
2019 ◽  
Vol 58 (12) ◽  
pp. 2143-2152 ◽  
Author(s):  
Yasuoki Horiike ◽  
Yuzo Suzuki ◽  
Tomoyuki Fujisawa ◽  
Hideki Yasui ◽  
Masato Karayama ◽  
...  
Keyword(s):  
Fatal Case ◽  
Mannose Receptor ◽  
Rank Test ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Macrophage Mannose Receptor ◽  
Potential Biomarker ◽  
Adjusted Logistic Regression ◽  
And Gender ◽  
Alternatively Activated

Abstract Objectives Macrophage-mannose receptor, CD206, is a marker of alternatively activated macrophages. Activated macrophages play key roles in DM. Interstitial lung disease (ILD) is a leading cause of mortality in patients with DM/clinically amyopathic DM (CADM). In particular, patients with the anti-melanoma differential gene 5 antibody (MDA5) frequently develop fatal rapid progressive ILD. This study aimed to evaluate the clinical implications of alternatively activated macrophages in patients with CADM/DM-ILD with anti-MDA5 antibody (MDA5-CADM/DM-ILD). Methods We measured serum concentrations of soluble CD206 (sCD206) in 33 patients with MDA5-CADM/DM-ILD and 36 age- and sex-matched control subjects. Expression levels of CD206 in the lungs from MDA5-CADM/DM-ILD were also examined. Results Patients with MDA5-CADM/DM-ILD had higher levels of sCD206 than those in controls (P < 0.0001). Of the 33 patients, 10 MDA5-CADM/DM-ILD patients developed fatal respiratory failure. Concentrations of sCD206 in patients with fatal ILD cases were significantly higher than those in the survivors, and increased sCD206 levels were associated with a higher mortality rate (Log-rank test, P = 0.0009). Age- and gender-adjusted logistic regression analyses showed that sCD206 was an independent prognostic factor for MDA5-CADM/DM-ILD. Importantly, assessment by sCD206 together with PaO2 successfully divided into three groups by their prognosis (P < 0.005, respectively). Pathological analyses showed accumulations of CD206-positive macrophages in lungs from the fatal case rather than those in the non-fatal cases. Conclusions Levels of serum sCD206 are increased in MDA5-CADM/DM-ILD and associated with poor prognosis. sCD206 is a potential biomarker to predict the severity of MDA5-CADM/DM-ILD.

scholarly journals DOP83 Intestinal fibrosis in Crohn’s disease patients is marked by up-regulation of innate immune cells and mucosal B cells

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S122-S123
Author(s):  
B Creyns ◽  
D Gabriele ◽  
C Jonathan ◽  
B Verstockt ◽  
G Bislenghi ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
B Cells ◽  
Crohn's Disease ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Intestinal Fibrosis ◽  
Fibrotic Tissue ◽  
Adaptive Immune Cells ◽  
And Control

Abstract Background Intestinal fibrosis represents a significant complication of inflammatory bowel disease (IBD). An urgent need is present for the identification of pathways and markers involved in fibrogenesis to prevent and intervene with intestinal fibrosis. As intestinal fibrosis mainly occurs in the intestinal deeper layers, mucosal biopsies for studies in intestinal fibrosis are of limited information. Therefore, characterisation of the relative contribution of innate and adaptive immune cells in the mucosa and deeper layers in fibrotic distal ileum of Crohn’s disease (CD) patients was performed. Methods Seventeen CD patients undergoing right hemicolectomy (RHC) for stricturing disease and 6 colorectal cancer (CRC) patients undergoing RHC were recruited. The resected ileum was divided in macroscopically inflamed and fibrotic tissue and single-cell suspensions were made from mucosal and deeper intestinal layers for immune cell characterisation with flow cytometry. For comparison, proximal unaffected CD tissue and control ileum from CRC patients was included. Fibrosis and inflammation were confirmed on HE stained histological sections. Wilcoxon matched-pairs signed-rank test between CD samples and Kruskal–Wallis testing with Dunn’s multiple comparisons test compared with CRC ileum were performed. Results From 12 CD patients, an additional macroscopically inflamed region could be identified next to the fibrotic area, with a decreased fibrosis score as compared with the fibrotic area (4.00 vs. 6.00, p = 0.016) (Figure 1). Both fibrotic and inflamed regions had increased inflammation as compared with proximal unaffected CD and control non-IBD ileum (score: 4.00 and 4.50 vs. 1.00 and 0.00, p &lt; 0.001 for all). In the inflamed ileum, no differences in immune populations were observed between mucosa and deeper layers, reflecting the transmural nature of CD. In contrast, CD19+ B cells were specifically enriched in the mucosa of fibrotic ileum, as compared with proximal CD mucosa (32.20 vs. 20.40% of CD45+ cells, p = 0.008) (Figure 2). In the deeper layers of fibrostenotic CD ileum FcεR+ Siglec 8+ eosinophils (1.13 vs. 1.17 % of CD45+ cells, p = 0.027), mature CD11c+ dendritic cells (3.95 vs. 2.96 % of CD45+ cells, p = 0.042) and M2 CD206+ macrophages (0.35 vs. 0.18% of CD45+ cells, p &lt; 0.001) were enriched as compared with the mucosa overlying the fibrotic tissue (Figure 3). Conclusion These results argue that inflammation in the deeper intestinal layers is different from the inflammatory signature seen in mucosal inflamed regions. We here report alternative innate immune cells expanded specifically in the deeper intestinal layers of fibrostenotic CD ileum that could identify targets for new anti-fibrotic therapies.

scholarly journals Probiotic Lactobacillus and Bifidobacterium Strains Counteract Adherent-Invasive Escherichia coli (AIEC) Virulence and Hamper IL-23/Th17 Axis in Ulcerative Colitis, but Not in Crohn’s Disease

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1824
Author(s):  
Gabriella Leccese ◽  
Alessia Bibi ◽  
Stefano Mazza ◽  
Federica Facciotti ◽  
Flavio Caprioli ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Dendritic Cells ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Immune Cells ◽  
Intestinal Epithelial ◽  
Healthy Donors ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Probiotic Strains

Hypersecretion of proinflammatory cytokines and dysregulated activation of the IL-23/Th17 axis in response to intestinal microbiota dysbiosis are key factors in the pathogenesis of inflammatory bowel diseases (IBD). In this work, we studied how Lactobacillus and Bifidobacterium strains affect AIEC-LF82 virulence mechanisms and the consequent inflammatory response linked to the CCR6–CCL20 and IL-23/Th17 axes in Crohn’s disease (CD) and ulcerative colitis (UC) patients. All Lactobacillus and Bifidobacterium strains significantly reduced the LF82 adhesion and persistence within HT29 intestinal epithelial cells, inhibiting IL-8 secretion while not affecting the CCR6–CCL20 axis. Moreover, they significantly reduced LF82 survival within macrophages and dendritic cells, reducing the secretion of polarizing cytokines related to the IL-23/Th17 axis, both in healthy donors (HD) and UC patients. In CD patients, however, only B. breve Bbr8 strain was able to slightly reduce the LF82 persistence within dendritic cells, thus hampering the IL-23/Th17 axis. In addition, probiotic strains were able to modulate the AIEC-induced inflammation in HD, reducing TNF-α and increasing IL-10 secretion by macrophages, but failed to do so in IBD patients. Interestingly, the probiotic strains studied in this work were all able to interfere with the IL-23/Th17 axis in UC patients, but not in CD patients. The different interaction mechanisms of probiotic strains with innate immune cells from UC and CD patients compared to HD suggest that testing on CD-derived immune cells may be pivotal for the identification of novel probiotic strains that could be effective also for CD patients.

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